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Infectious and inflammatory diseases: our research

Microbial infections and inflammatory diseases remain major causes of mortality and morbidity worldwide. One in four deaths is due to infections, a proportion twice as high as the mortality rate from cancer.

The incidence is even higher in children, where infectious diseases are the leading cause of death. Their long-term impact on other conditions such as cancers, cardiovascular, metabolic, and neurodegenerative diseases is considerable.

Understanding infection and immunity, including its dysregulations, requires multidisciplinary and integrated approaches which are being developed within the Centre for Infection and Immunity in Lille (CIIL).

The 14 teams of the CIIL bring together nearly 230 researchers, engineers, technicians and students with complementary expertise that cover a wide range of disciplines, from molecular epidemiology, virology, bacteriology and molecular and cellular parasitology, to the immunological bases of infectious and non-infectious diseases and the development of clinical applications.

The researchers' objective is to contribute to the development of innovative approaches in the areas of diagnosis, treatment and prevention (vaccine) of these diseases while analyzing their impact on the ground.

Research at the Pasteur Institute of Lille

At the Lille Center for Infection and Immunity, scientists study bacterial, viral, and parasitic diseases and the immune response to these infections, as well as immune dysfunctions associated with non-infectious diseases such as allergic asthma and chronic obstructive pulmonary disease (COPD). The teams also work on opportunistic infections in the context of cystic fibrosis, the most common human genetic disease. The main infectious diseases studied include tuberculosis, pneumococcal pneumonia, pertussis (whooping cough), plague, hepatitis C, hepatitis E, influenza, Middle East Respiratory Syndrome (MERS), COVID-19, malaria, schistosomiasis, toxoplasmosis, cryptosporidiosis, and blastocystosis.

Coronavirus and COVID-19

Specializing in molecular and cellular virology, Dr. Jean Dubuisson's team has been working for several years on coronaviruses, such as MERS-CoV and SARS-CoV-2, the virus responsible for the COVID-19 pandemic. Research at the Pasteur Institute of Lille aims to characterize the interactions of coronaviruses with cells in order to better understand their viral cycle and identify antiviral targets. The goal is to develop therapeutic approaches against emerging coronaviruses. Other teams at the CIIL (Interdisciplinary Center for Clinical and Laboratory Research) are also working on this virus, notably that of Dr. François Trottein, who is developing preclinical models to study the potential efficacy of drug candidates and to better understand the pathophysiology of COVID-19.

In response to the COVID-19 pandemic, the Pasteur Institute of Lille mobilized a dedicated “Task Force” team to:

  • To identify as quickly as possible, from a collection encompassing all drugs used worldwide, those that can inhibit this virus.
  • Finding therapeutic weapons for future coronavirus epidemics, by targeting specific components of the virus.
  • Developing vaccination platforms for better protection of the population.

The Whooping Cough

Research is focused on developing a nasal vaccine that should allow young children to be vaccinated from birth and protect them when they are most vulnerable (team of Dr. Nathalie Mielcarek and Camille Locht). The vaccine candidate is a genetically attenuated strain of Bordetella pertussis whose efficacy has been experimentally proven. Administered by painless instillation of a nasal drop, the vaccine is currently being evaluated in humans and could be used worldwide.

Bacterial superinfections

Researchers are studying in the laboratory the mechanisms of immunity that make some individuals with the flu more susceptible to bacterial infections, or certain particularly virulent forms of the flu.

Dr. François Trottein's team recently demonstrated that the gut microbiota plays a key role in this infection. Thus, by strengthening the properties of this microbiota, we would be better protected against the flu and its complications, particularly bacterial superinfections. " explains François Trottein.

Hepatitis E

Dr. Jean Dubuisson's team is conducting research on the biology of the hepatitis E virus.It is difficult to propagate this virus in cell culture, and we have developed a cell culture system to study the interactions between the hepatitis E virus and its host. The fundamental knowledge we hope to accumulate about this virus should help us develop antiviral molecules to combat severe forms of this viral infection.“Jean Dubuisson points out.

Malaria

The team led by Dr. Jamal Khalife is studying the molecular and cellular mechanisms involved in the growth and differentiation of the Plasmodium parasite in order to propose new ways to control malaria.

For several years, the team has been studying Plasmodium enzymes involved in chromatin remodeling and histone modifications. The team has identified several particularly active molecules whose efficacy has also been demonstrated in a preclinical model.

Dr. Sylviane Pied's team is investigating the immune response during primary infection with Plasmodium falciparum. These studies combine basic and clinical research in cohorts of African and Indian patients. Fieldwork is conducted through a collaborative network, notably in Gabon and India.

Toxoplasmosis

This parasitic disease is one of the most widespread in the world, affecting more than a third of the global population. It is caused by a parasite, Toxoplasma gondii, transmitted through contaminated food or water. T. gondii infection is a major cause of neonatal morbidity and mortality and can be fatal in immunocompromised patients (AIDS, transplant recipients, or those with certain cancers).

Currently, few molecules effectively combat this parasite, and some parasitic forms remain completely untreatable, particularly latent forms found in the brain and muscles. Drs. Sabrina Marion and Mathieu Gissot are studying the parasite's biology, especially its ability to proliferate. The researchers are also trying to understand how the immune system responds to the infection in order to identify new vaccine avenues.

The Plague

Within the framework of potentially emerging diseases, teams at the Pasteur Institute in Lille are working on rare pathogens that could trigger epidemics. The team led by Dr. Florent Sebbane is working on the molecular mechanisms of plague transmission. More specifically, it is seeking to identify the genes that allow the bacterium to be efficiently transmitted by fleas, as well as those responsible for the disease in mammals. The aim is to propose effective preventative measures in case of a resurgence of this highly contagious disease. "Florent Sebbane tells us.

Regarding inflammatory diseases, the CIIL specializes in pulmonary pathologies. Anne Tsicopoulos's team works on allergic asthma, both in humans and in preclinical models. Furthermore, Dr. Philippe Gosset's team focuses on chronic obstructive pulmonary disease (COPD), a highly debilitating disease affecting more than 10% of the population in France. The objectives of our research are to better understand the pathophysiology of these diseases and ultimately to propose relevant and innovative treatments. "The two researchers told us.

Other infectious diseases are studied at the CIIL, including tuberculosis (Priscille Brodin, Alain Baulard), pneumococcal pneumonia (Jean Claude Sirard), schistosomiasis (Oleg Melnyk), cryptosporidiosis, and blastocystosis (Eric Viscogliosi). Scientists seek to better understand the biology of pathogens and how the body reacts to them. This integrated research aims to identify innovative new therapeutic approaches. In this context, the search for new antibiotics is particularly active. For example, Dr. Ruben Hartkoorn's team (ERC) is working to identify new antibiotics and develop innovative strategies to improve antibiotic penetration into bacteria.

The Human Immunodeficiency Virus (HIV)

The agent responsible for AIDS has been a major public health problem for over 40 years. HIV causes immunosuppression in the host through infection, multiplication, and persistence in myeloid and lymphoid immune cells, which can transform into viral reservoirs. Dr. Fernando Real's team aims to detect and better characterize these cells, particularly myeloid cells such as macrophages and megakaryocytes, and to understand the cellular and molecular mechanisms underlying their maintenance and their deleterious effect on the immune system. The team is investigating whether viral reservoirs are inflammatory cells that support the production of viruses and viral components that compromise the function and generation of new immune cells. This research could open new therapeutic avenues for treating persistent viral infections and their long-term consequences.

INTHREPIDE: our program to combat epidemic risks and antibiotic resistance

Recent pandemics demonstrate the urgent need for our societies to equip themselves with the means for a very strong response to the emergence of pathogens that could destabilize them.

The INTHREPIDE research program, launched by researchers at the Pasteur Institute of Lille, aims to identify new therapeutic principles against emerging viral infections and infections by multi-resistant bacteria.

The research teams

U1019 – UMR9017

Lille Infection and Immunity Center

University of Lille, CNRS, Inserm, Pasteur Institute of Lille, Lille University Hospital

Director: Frank LAFONT