Montreal researchers identify defects of immune cells

Researchers at Université de Montréal and the Institut de recherches cliniques de Montréal (IRCM) have successfully identified a defective immune cell population that determines susceptibility to candidiasis, a common and often debilitating infection in individuals infected with the human immunodeficiency virus (HIV). These findings, revealed using a model of candidiasis in transgenic mice expressing HIV developed by the same research group, represents a milestone in developing a treatment for the infection and, eventually, preventing it. They are described in an article of the July 1st issue of The Journal of Immunology.

Oral and esophageal Candida albicans infections, which often affect individuals infected with HIV, may limit food consumption and lead to weight loss, threatening patients' general health and well-being. Of added concern, treatment of candidiasis in these patients is often complicated by strains of Candida albicans resistant to conventional antifungal therapies. The research project was carried out jointly by Dr. Louis de Repentigny, Director of the Medical Mycology Laboratory and Professor in the Department of Microbiology and Immunology at the Faculty of Medicine of Université de Montréal, and at CHU Sainte-Justine, and Dr. Paul Jolicoeur, Director of the Molecular Biology Research Unit at the Institut de recherches cliniques de Montréal (IRCM), researcher in the Department of Microbiology and Immunology at the Faculty of Medicine of Université de Montréal, associate member of the McGill University Faculty of Medicine and holder of the Canada Research Chair on Infectious and Parasitic Diseases and Dr Zaher Hanna, Associate Director in the same Unit, researcher in the Department of Medicine at the Faculty of Medicine of Université de Montréal, associate member of the McGill University Division of Experimental Medicine.

Drs de Repentigny, Jolicœur and Hanna have for the first time succeeded in demonstrating that defective CD4+ T lymphocytes primarily determine the susceptibility to oral candidiasis in transgenic mice expressing HIV-1 and developing an AIDS-like disease. Findings from this research further indicated that a diminution and functional defects of both dendritic cells and CD4+ cells cause susceptibility to candidiasis in these transgenic mice by preventing T lymphocyte mediated acquired immunity to Candida albicans. The results also showed extensive perturbations in the production of cytokines required for protection against oral candidiasis in the transgenic mice.

“These findings regarding the specific immune defects which trigger candidiasis are very promising,” explains Dr. de Repentigny. “This new knowledge will be instrumental in designing more powerful and effective treatments, which will directly improve the health status of HIV-infected patients who suffer from candidiasis. Defective CD4+ T lymphocytes have long been suspected to be the leading cause of candidiasis, however, it never had been directly demonstrated. Now, they become designated targets for the development of novel treatments not only for candidiasis but other mucosal infections.”

“Secondary infections are the major cause of morbidity and mortality in people infected by HIV/AIDS. Fungal infection due to candidiasis is one of these debilitating conditions,” said Dr. Bhagirath Singh, Scientific Director of the Canadian Institutes of Health Research (CIHR) Institute of Infection and Immunity. “This work provides a new understanding of why candidiasis is not controlled by the body's immune cells, particularly the CD4+ T lymphocytes. It will also help us to develop better treatments to prevent these opportunistic infections in HIV patients.”