Presence of hepcidin (in brown) in the epidermis of a patient with pustular psoriasis. © Élise Abboud

Psoriasis is a chronic inflammatory disease characterised by the rapid and excessive multiplication of skin cells. Although research is progressing and certain treatments are already able to improve the daily lives of patients, this disease remains incurable. The team led by Carole Peyssonnaux, Inserm Research Director at Institut Cochin (Inserm/CNRS/Université Paris Cité) has shown that a hormone that regulates iron in the body, called hepcidin, is produced by the patients’ skin and is essential for triggering psoriasis. This discovery opens up new avenues for treatment. Drugs that block the action of hepcidin could be a therapeutic alternative in psoriasis. These findings have been published in Nature Communications.

Psoriasis is a chronic inflammatory disease that primarily affects the skin. It is common and affects 2 to 3% of the world’s population. Despite many treatment options available to improve patient care, psoriasis remains a chronic condition with no definitive cure.

Characterised by red patches covered with scales, the disease manifests as an excessive proliferation of epidermal cells and an excess of immune cells in the skin, accompanied by a local inflammatory reaction.

Over the last few decades, much progress has been made in understanding the disease, such as the identification of certain genetic factors. Several studies, whose findings are still little known by the scientific community, have also shown that there is an accumulation of iron in the skin of psoriasis patients. We know that the regulation of iron levels in the body is controlled by a hormone called hepcidin. While hepcidin is primarily synthesised by the liver, it can be produced by other organs or tissues under disease conditions.

For years, the Iron and Immunity team at Institut Cochin, led by Inserm Research Director Carole Peyssonnaux, has studied hepcidin closely. Despite the proven presence of iron in the epidermis of psoriasis patients, the production by the skin and the potential role of this ‘iron hormone’ in psoriasis had never been investigated. The researchers therefore decided to study this avenue more closely.

The team[1] started by showing that hepcidin was expressed in the skin of patients with psoriasis, particularly in severe forms such as pustular psoriasis, which is characterised by the accumulation of a type of white blood cell – neutrophils – within the epidermis.

To further study the role of hepcidin in psoriasis, the team then developed new mouse models in which the hepcidin gene was specifically inactivated or overexpressed in the epidermis. The scientists then showed that when this gene was activated, certain characteristics of psoriasis were induced, including skin lesions and the recruitment of neutrophils in the epidermis. Conversely, when the gene was inactivated, the psoriasis markers disappeared.

‘Hepcidin plays a key role in the development of psoriasis. Based on our findings, we show that when psoriasis is triggered, the hepcidin produced by the epidermis plays a crucial role in retaining iron in the skin cells. With iron being an essential metal for cell proliferation, this retention promotes cell division in the epidermis of “psoriatic” skin. What is more, hepcidin-mediated iron retention also contributes to the recruitment of neutrophils, another characteristic of psoriatic skin lesions, particularly pustular’, explains Peyssonnaux.

The next step would be to explore these findings in greater depth, with the goal of developing drugs to block the action of hepcidin and therefore potentially benefit patients with psoriasis, particularly those suffering from an acute and resistant form. With this in mind, the team is developing, with the support of Inserm Transfert[2], new drugs capable of neutralising hepcidin, in order to test them in animal models of psoriasis.

‘In the future, if our findings prove conclusive, such drugs could be used as maintenance therapy following a flare-up, during phases of remission, to prevent recurrence of the disease. Additional studies will determine whether hepcidin also plays a role in other inflammatory skin diseases’, concludes Peyssonnaux.

[1]In collaboration with the team of Selim Aractingi (Cochin Hospital) and Hervé Bachelez (Saint-Louis Hospital)

[2] Patent WO2016/146587 / EP3268027B1 and US11203753B2

Vaccination © Inserm/Depardieu, Michel

The ANRS DOXYVAC trial, promoted and funded by ANRS Emerging Infectious Diseases, and conducted by research teams from Inserm, AP-HP, Université Paris Cité and Sorbonne Université (France), shows that a rapid rollout of smallpox vaccination with MVA-BN (Modified vaccine Ankara) among HIV-positive men who have sex with men significantly reduces the risk of mpox by 99%. The results of this study were published in The Lancet Regional Health-Europe on 31 July 2024.

In May 2022, cases of mpox, formerly known as monkeypox, were reported in more than 100 countries where the disease was not endemic. In France, the first case was reported on 19 May, with a rapid increase in infections among men who have sex with men (MSM).

The ANRS DOXYVAC trial, which began in 2021, was designed to study how to improve protection against sexually transmitted infections (STIs) in HIV-positive men who have sex with men.* So, when it became apparent during the course of the study that mpox cases could occur in the trial population, a smallpox vaccination was conducted, as soon as preventive  vaccination in multi-partner MSM was recommended  by French Health Authorities (HAS) on 11 July 2022.

To date, there is no specific vaccine against mpox. However, the virus is closely related to that of human smallpox, and the smallpox vaccine has been shown to be more than 95% effective in protecting against mpox. The vaccine used in the trial, Imvanex® (MVA-BN: Modified vaccine Ankara) from Bavarian Nordic, is a third-generation vaccine. This type of vaccine is produced from smallpox virus with the same antigens as historical smallpox. More specifically, it contains a highly attenuated form of the vaccinia virus known as “modified vaccinia virus Ankara”, a virus that does not cause disease in humans and cannot reproduce in the cells of people who are vaccinated. This means that the vaccine cannot cause local or systemic infections, particularly in immunocompromised people (such as those infected with HIV).

The aim of the analysis among participants of the ANRS DOXYVAC trial was to assess the incidence of mpox infection in participants before (9 May-10 July 2022) and after the launch of the MVA-BN vaccination campaign (from 11 July 2022), and to study the respective effects of vaccination and sexual behaviour adopted during the epidemic period on changes in incidence.

Of the 472 participants included in the analysis, 20% had been vaccinated against smallpox in childhood. The incidence rate** of mpox among trial participants, all of whom were on HIV pre-exposure prophylaxis (PrEP) and had a history of bacterial STIs, was high (49.3 per 1,000 participant-months between 9 May and 20 September 2022).

Vaccination implementation was rapid: 86% (341/398) of eligible participants had received at least one dose of MVA-BN vaccine by 20 September 2022. People were also particularly receptive to the prevention messages and recommendations, especially those with more than ten sexual partners in the last three months who are most at risk. Their sexual behaviour changed significantly before and after 9 May, leading to a reduction in the proportion of people with more than 10 partners in the last 3 months (45% compared with 38%). A significant reduction in the incidence rate of mpox was observed between the period prior to vaccination (67.4 per 1,000 months between May 9 and July 10, 2022) and the period following the launch of the vaccination campaign (24.4 per 1,000 months between July 11 and September 20, 2022).

This trial demonstrated that the rapid implementation of smallpox vaccination with MVA-BN in MSM undergoing PreP significantly reduced the risk of mpox, with an estimated 99% reduction in incidence between the two periods. The reduction in risky sexual behaviour among those most at risk also probably contributed to the reduction in incidence, but to a lesser extent than the vaccination programme.

This study emphasises that identifying and prioritising at-risk populations, delivering targeted prevention messages and awareness campaigns, ensuring the availability of a smallpox vaccine and, above all, the rapid rollout of vaccination to people at risk should enable health authorities to control a future mpox epidemic like the one that occurred in 2022.

* DOXYVAC has demonstrated the efficacy of post-exposure doxycycline in reducing the occurrence of chlamydial infections, syphilis and, to a lesser extent, gonococcal infections.

** Incidence is the number of new cases of a disease in a year in a given population (not to be confused with prevalence, which refers to the number of sick people at a given time). The incidence rate of a disease corresponds to the number of individuals having contracted a disease per 1,000 people exposed to the risk of this disease (in the DOXYVAC trial, it is calculated for one month) (https://www.ined.fr/en/glossary/incidence-of-a-disease/).

Marking of cytotoxic T cells (CD8 in red and the ‘residence’ marker CD103 in green) lodged in the choroid plexus of a brain infected with the parasite Toxoplasma gondii. © Amel Aida

Toxoplasmosis is an infection caused by the parasite Toxoplasma gondii (T. gondii). In over one third of the human population, this parasite establishes a chronic infection of the brain which can have serious consequences in people with compromised immunity. Given the current lack of treatment to eliminate the persistent form of the parasite, a deeper insight into the immune mechanisms controlling this infection is essential if we are to hope to develop new therapeutic strategies. The study, conducted by Inserm researcher Nicolas Blanchard and his team at the Toulouse Institute for Infectious and Inflammatory Diseases (Infinity, Université Toulouse III Paul Sabatier, CNRS, Inserm), has shown that a category of immune cells known as resident CD8+ T cells plays a key role in detecting and neutralising the toxoplasmosis parasite in the brain. These findings, published in PNAS, make it possible to envisage new avenues for treatments to eliminate the persistent forms of toxoplasmosis.

Toxoplasmosis is a very common parasitic infection in humans. One in three people – or even one in two in some countries – has been exposed to this parasite in their lifetime. The parasite is transmitted by direct contact with the faeces of a feline carrier of T. gondii or by eating foods contaminated with it (poorly cooked meat, raw fruit and vegetables).

The consequences of this infection vary from one person to another. In healthy people, these are usually mild: while there may be fever and fatigue, the symptoms often go unnoticed. However, the parasite is not eliminated from the body. It can persist permanently in a so-called ‘latent’ form in the muscles, retina and brain. A growing body of data suggests that this chronic brain infection is associated with behavioural changes, or even an acceleration of neurodegenerative phenomena. What is more, in people with more fragile immunity, such as those with AIDS or using certain immunosuppressive treatments (e.g. in case of transplant), the consequences can be severe because the parasite can reactivate in the brain and cause potentially fatal inflammation (called brain toxoplasmosis or neurotoxoplasmosis).

At present, there is no treatment to eliminate the persistent form and permanently remove the parasite. A better understanding of the immune mechanisms that control the parasite, particularly in the brain, could suggest new therapeutic strategies aimed at stimulating natural immunity to the parasite in order to better contain or even eliminate it. 

The research team had previously shown that specific immune cells, called CD8+ T cells or ‘killer’ T cells, play a key role in controlling the parasite in the brain. However, we are dealing with a very diverse population of cells. For Inserm researcher Nicolas Blanchard and his team, it was crucial to identify which CD8+ T-cell subtype is involved, in order to elucidate the immune surveillance mechanisms of the parasite in the brain.

In 2009, a specific subtype of CD8+ T cells, referred to as ‘resident’ CD8+ T cells, was discovered.  These cells have the particularity of not patrolling the body but remaining stationary in the tissues, particularly the brain. The role of the brain-resident CD8+ T cell subpopulations in neutralising and eliminating the parasite had never previously been studied.

To study this role, the researchers used an animal model that mimics the latent T. gondii infection found in humans. Through selective elimination of the circulating or resident subpopulations, the team showed that the parasite is controlled in the brain by resident CD8+ T cells, as opposed to the other lymphocytes that patrol the lymphoid organs and tissues.

The researchers have also shown that the resident CD8+ T cells form thanks to signals issued by other immune cells, namely CD4+ T cells.

‘This is an interesting finding because it gives us a deeper insight into why people with HIV are potentially more vulnerable to brain toxoplasmosis. Indeed, HIV is known to reduce the number of CD4+ T cells, which could have a negative impact cascade on the formation of brain-resident CD8+ T cells, and therefore alter immunity to the toxoplasmosis parasite,’ explains Blanchard.

Based on these findings, the scientists will now be able to consider strategies in an attempt to improve the capacity of resident lymphocytes to fight brain infection.

‘Now that we have a better understanding of the mechanisms of surveillance of the toxoplasmosis parasite in the brain, we are conducting other research to understand the mechanisms deployed by the parasite to evade the control by CD8+ T cells and how we can try to neutralise these mechanisms,’ concludes Blanchard.

Microscopic visualisation of immune cells (in green) activated by the alarmins TL1A and interleukin-33 during the onset of allergic inflammation in the lungs. ILC2s immune cells produce large quantities of interleukin-9, a key mediator of allergic inflammation. They are located near collagen fibres (blue) and blood vessels in the lung (red). © Jean-Philippe GIRARD – IPBS (CNRS/UT3 Paul Sabatier).

One of the molecules responsible for triggering the inflammation that causes allergic respiratory diseases, such as asthma and allergic rhinitis, has just been discovered by scientists from the CNRS, Inserm and the Université Toulouse III – Paul Sabatier. This molecule, from the alarmin family, represents a therapeutic target of major interest for the treatment of allergic diseases. The study, co-directed by Corinne Cayrol and Jean-Philippe Girard, is published in the Journal of Experimental Medicine on 10 April¹.

The inflammation process plays a crucial role in allergic respiratory diseases, such as asthma and allergic rhinitis. Although the pulmonary epithelium, the carpet of cells that forms the inner surface of the lungs, is recognised as a major player in the respiratory inflammation that causes these diseases, the underlying mechanisms are still poorly understood.

A research team has identified one of the molecules responsible for triggering these allergic reactions, in a study co-led by two CNRS and Inserm scientists working at l’Institut de pharmacologie et de biologie structural (CNRS/Université Toulouse III – Paul Sabatier). This molecule from the alarmin family, named TL1A, is released by lung epithelium cells a few minutes after exposure to a mould-type allergen. It cooperates with another alarmin, interleukin-33, to alert the immune system. This double alarm signal stimulates the activity of immune cells, triggering a cascade of reactions responsible for allergic inflammation.

Alarmins, therefore, constitute major therapeutic targets for the treatment of respiratory allergic diseases. In a few years’ time, treatments based on antibodies blocking the TL1A alarmin could benefit patients suffering from severe asthma or other allergic diseases. In France, at least 17 million people are affected by allergic diseases² with the most severe forms of asthma being responsible for several hundred deaths every year³.

1. This study was supported by the ANR.
2. According to the Ministère du travail, de la santé et des solidarités : https://sante.gouv.fr/sante-et-environnement/air-exterieur/pollens-et-allergies/article/effets-des-pollens-sur-la-sante; 13/04/2023
3. According to Santé Publique France : https://www.santepubliquefrance.fr/maladies-et-traumatismes/maladies-liees-au-travail/asthme; 25/10/2023

 HIV 3d illustration © Adobe Stock

People living with HIV need to take antiretroviral treatment for life to prevent the virus from multiplying in their body. But some people, known as “post-treatment controllers,” have been able to discontinue their treatment while maintaining an undetectable viral load for several years. Starting treatment early could promote long-term control of the virus if treatment is discontinued. Scientists from the Institut Pasteur, the CEA, Inserm, Université Paris Cité and Université Paris-Saclay, in collaboration with Institut Cochin[1] and with the support of MSD Avenir and ANRS Emerging Infectious Diseases, used an animal model to identify a window of opportunity for the introduction of treatment that promotes remission of HIV infection: it appears that starting treatment four weeks after infection promotes long-term control of the virus following the interruption of treatment after two years of antiretroviral therapy. These results highlight how important it is for people with HIV to be diagnosed and begin treatment as early as possible. The findings were published in the journal Nature Communications on January 11, 2024.

Antibody fragments of EPCT112 bNAb (blue) discovered at the Institut Pasteur by Hugo Mouquet’s team, here forming a complex with the HIV-1 envelope protein (Env) (shown in yellow and orange

Some HIV-1 carriers who have received an early antiretroviral treatment during several years are able to control the virus for a long term after treatment interruption. However, the mechanisms enabling this post-treatment control have not been fully elucidated. For the first time, teams of scientists from the Institut Pasteur, Inserm and the Paris Public Hospital Network (AP-HP), supported by ANRS | Emerging Infectious Diseases, have investigated and revealed how neutralizing antibodies, including those described as broadly neutralizing, contribute to virus control. These key findings were published in the journal Cell Host & Microbe on July 10, 2023. A clinical trial involving the use of broadly neutralizing antibodies should begin in France before the end of 2023.

“Post-treatment controllers” is the term used to describe the rare HIV-1 carriers who, having initiated treatment early and maintained it for several years, are able to control the virus for years after that the treatment has been discontinued. These individuals were identified several years ago in part through the VISCONTI[1] study, which assembled the largest cohort of long-term post-treatment controllers in France. Although the mechanisms of viral control enabling the long-term remission from HIV-1 infection without antiretroviral therapy have not been fully elucidated, the identification of these cases provides a unique opportunity to refine our understanding of the factors associated to HIV-1 infection control.

A study conducted by the Institut Pasteur’s Humoral Immunology Unit led by Dr. Hugo Mouquet in collaboration with the team led by Dr. Asier Sáez-Cirión, Head of the Institut Pasteur’s Viral Reservoirs and Immune Control Unit, is now contributing to efforts to describe these mechanisms in more detail.

Asier Saéz-Cirión explains: “Our investigation published in 2020 on the immune response in post-treatment controllers marked a major first step in demonstrating an effective and robust antibody response to HIV-1 in some of these individuals, which may contribute to this control[2].This knowledge has now been further advanced by our new study. By investigating the role of antibodies in a specific “post-treatment controller” case with particularly high serum levels of broadly neutralizing antibodies, we discovered that remission was probably linked to the activity of this type of antibodies.”

Hugo Mouquet describes the discovery: “Our study describes for the first time in a post-treatment controller a family of broadly neutralizing antibodies (bNAbs) targeting the HIV-1 envelope protein, of which the antibody EPTC112 is one of the most active member.“

The antibody EPTC112 neutralizes about a third of the 200 viral variants of HIV-1[3] tested in vitro and is able to induce the elimination of infected cells in the presence of natural killer (NK) cells, the immune cells eliminating abnormal cells in the body.

This study therefore provides important insights on how neutralizing antibodies modify the course of HIV-1 infection in this individual from the VISCONTI cohort. Although the HIV-1 virus circulating in this subject was found to be resistant to EPTC112 neutralization due to mutations in the region targeted by this antibody, it was effectively neutralized by other antibody populations isolated from the blood of the individual. Hence, the study suggests that neutralizing antibodies from the EPTC112 family impose a selective pressure on the HIV-1 virus. Although the virus escaped the action of these bNAbs, it remained susceptible to the neutralization by other anti-HIV-1 antibodies produced in this individual. This observation suggests the existence of a cooperation between the various populations of neutralizing antibodies.

“The fact that we discovered a potential link between the production of neutralizing antibodies, including bNAbs, and the HIV-1 control is exciting to better understand the underlying mechanisms of viral control, particularly by studying additional post-treatment controllers with similar profiles. Indeed, we wish to continue investigating on a short term whether the antibody responses in other ‘post-treatment’ controllers also contribute to long-term remission from the infection,” explains Hugo Mouquet.

This discovery paves the way for new avenues of HIV-1 therapy and fuels hopes of therapeutic approaches for increasing the chances of remission without antiretroviral treatment through the use of broadly neutralizing antibodies. To this end, a clinical trial involving the administration of broadly neutralizing antibodies[4] should begin in France before the end of 2023.

“This Phase II trial conducted by the ANRS RHIVIERA consortium through a partnership between the Institut Pasteur, AP-HP, Inserm and the Rockefeller University in New York, will investigate the combination of an antiretroviral therapy in the primary infection phase with two long-acting HIV-1 bNAbs versus placebo to determine whether these antibodies contribute to establishing viral remission after antiretroviral treatment discontinuation. 69 patients in the primary HIV-1 infection[5] phase are planned to be enrolled. They will first receive a short-term antiretroviral treatment, followed by a therapy with the two bNAbs targeting two different regions of the virus envelope protein. It will be possible to stop therapy after a year of close monitoring based on a detailed set of criteria. This trial will enable us to determine whether this therapeutic strategy is able to induce a sufficient immune response to control the infection after the discontinuation of antiretroviral therapy,” concludes Hugo Mouquet.

Antibody fragments of EPCT112 bNAb (blue) discovered at the Institut Pasteur by Hugo Mouquet’s team, here forming a complex with the HIV-1 envelope protein (Env) (shown in yellow and orange) © Institut Pasteur

[1] HIV: The Antibodies of “Post-treatment Controllers”

[2] Transient viral exposure drives functionally coordinated humoral immune responses in HIV-1 post-treatment controllers study, Nature Communication, 11 avril 2022

[3] There are two types of HIV: HIV-1 and HIV-2 that differ from each other at molecular level. Variants occurring within these two types exhibit different levels of transmissibility, virulence and immunogenicity due to the various mutations associated with them.

[4] https://rhiviera.com/project/anrs-rhiviera-02/

[5] Primary infection: early phase of HIV-1 infection during which the viral load is high. The HIV virus invades the body, attacking the immune system and destroying its CD4 lymphocyte reservoirs.

Immune system cell infected with Brucella (green); endocytosis compartment (blue). © CIML

Correct immune system function depends on the continuous supply of white blood cells derived from stem cells that reside in the bone marrow.  These are known as blood stem cells or hematopoietic stem cells. Researchers from Inserm, CNRS and Université d’Aix-Marseille at the Center of Immunology Marseille-Luminy have now discovered a new role played by these cells in immune response. In their article published in Journal of Experimental Medicine, they describe how they are able to recognize and directly interact with a bacterium called Brucella in the bone marrow, thanks to a receptor present on their surface. This is the first demonstration of the direct recognition of a living pathogen by the blood stem cells, which attests to their very early contribution to the immune response.

Blood stem cells, otherwise known as hematopoietic stem cells, are stem cells that reside in the bone marrow. They multiply and give rise to all blood cells, namely the red cells that transport oxygen and the white cells that participate in the immune response.

With regard to immune response, the blood stem cells had until now only been seen as the cells from which the white cells originate. However, a growing body of evidence suggests that they can also contribute directly and actively to the immune response. For example, recent data have shown that they can directly detect cytokines, which are proteins released during infection or inflammation.

In a new publication, a research team from Inserm, CNRS and Université d’Aix-Marseille led by Michael Sieweke and Jean-Pierre Gorvel[1] wanted to further the scientific knowledge in this area. The researchers succeeded in describing the mechanisms at work during the encounter between the blood stem cell and a specific pathogen: the Brucella bacterium, which is a mandatory reportable microorganism/toxin (MOT)[2].

Brucella causes an infectious disease called brucellosis (also known as Malta fever or Mediterranean fever), which is one of the most widespread zoonoses posing a significant threat to human health worldwide[3]. Brucella is an intriguing pathogen and very interesting for the scientists to study because of its ability to establish persistent and chronic infections and evade the immune response of its host[4].

The scientists found that the blood stem cells present in the bone marrow were able to detect Brucella. Their observations show that CD150, a specific receptor on the surface of the blood stem cells, interacts with Omp25, a protein present on the surface of Brucella.

Graphic Summary of the Discovery. Thanks to the CD150 receptor on their surface, the blood stem cells in the bone marrow are able to detect Brucella. After recognizing it, they begin to produce more white blood cells. © CIML

“Our study reveals the mechanisms by which these blood cells are able to detect bacteria via a special receptor. We can consider this as a direct ‘handshake’ between the stem cell and the bacterium. Never had anyone imagined that the blood stem cell could recognize a living bacterium,” explains Sandrine Sarrazin, Inserm researcher and co-last author of the study.

The scientists then showed that this “handshake” leads to a rapid response by the stem cells, whereby they begin to produce more white blood cells. This is the first demonstration of the direct recognition of a living pathogen by blood stem cells and attests to a very early and unexpected contribution of these cells to the immune response.

How Brucella Uses Stem Cells to “Hack” the Immune System

The scientists then wondered whether this mechanism was more beneficial to the host or to the bacterium.

Thanks to meticulous observations, they found that Brucella directs the stem cells to produce the white blood cells it favors for infection. The bacterium is able to invade the white blood cells produced by the blood stem cells and use them to multiply and establish itself in the body. In this particular case, the stem cells therefore contribute to the spread of the bacterium.

“This research sheds new light on the sophisticated mechanisms that pathogens use to evade the immune system’s defenses. While the increased production of white blood cells would be beneficial if they could effectively fight infection, Brucella is able to exploit them in order to multiply,” explains Gorvel, one of the co-last authors of the study.

“This mechanism can be seen as an evasion strategy used by the bacterium to advance the infection,” summarizes Sieweke, another co-last author of the study.

The publication of this study marks an important step in understanding the complex dance between Brucella and the hematopoietic stem cells. It not only provides crucial information on the pathogenesis of brucellosis, but also opens up new avenues for the development of targeted therapeutic interventions.

“In addition to improving knowledge about how the immune response works, our study ultimately allows us to envisage the development of a targeted therapy capable of preventing the interactions between Brucella and the blood stem cell, preventing the spread of the bacteria in the body and helping patients with brucellosis,” concludes Gorvel.

[1] This research is the result of a collaboration between two research teams at the Center of Immunology Marseille-Luminy (CIML, CNRS/Inserm/Aix-Marseille Université): Michael Sieweke’s Stem cell and macrophage biology team and Jean-Pierre Gorvel’s Immunology and cell biology of pathogen/host cell interactions team.

[2] The Brucella experiment was therefore conducted at the Center for Immunophenomics (CIPHE) under biosafety level 3 conditions.

[3] The World Health Organization (WHO) has identified brucellosis as being one of the seven most neglected zoonoses, contributing to poverty, hindering development, and causing substantial economic losses in developing countries.

[4] Previous studies conducted at Gorvel’s laboratory had enabled crucial discoveries with the aim of elucidating the mechanisms underlying these phenomena.