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Infections par SARS-COV-2 et par VIH-1 : activations immunitaires aigüe et chronique

Abstract : During an infection, the main purpose of the immune response is to eliminate the pathogen. However, this response can have chronic side effects, such as in people living with aviremic HIV on treatment or acute, as in severe forms of COVID-19.People living with HIV-1, despite effective antiretroviral therapy, have more comorbidities compared with the general population. Many of these comorbidities are linked to persistent immune activation. We showed that different immune activation patterns could be identified in these patients, one of which was associated with the presence of microbial translocation and another with residual viremia. We also showed that different immune activation patterns were visible in a cohort of people from the general population and that people with one of these patterns showed signs of insulin resistance and metabolic syndrome.In a context of SARS-COV-2 infection, lymphopenia is observed in some patients. This lymphopenia is a predictor of complications up to admission into intensive care units or death. This lymphopenia seems to occur before the cytokinetic storm and could be one of the causes. We discovered a potential explanation for this lymphopenia: the monocytes of some patients admitted to the hospital produce reactive oxygen derivatives responsible for DNA damage and then apoptosis in circulating lymphocytes. These reactive oxygen derivatives are produced because of stimulation via the AT1R receptor of monocytes by angiotensin II, whose blood concentration is increased probably due to internalization of ACE2, an enzyme capable of cleaving angiotensin II, induced by SARS-COV-2 during cellular entry.Our work allows us to better understand the pathogenic mechanisms due to the immune activation induced by two different viruses and thus opens up therapeutic perspectives.
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https://tel.archives-ouvertes.fr/tel-03431161
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Submitted on : Tuesday, November 16, 2021 - 3:11:28 PM
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Lucy Kundura. Infections par SARS-COV-2 et par VIH-1 : activations immunitaires aigüe et chronique. Médecine humaine et pathologie. Université Montpellier, 2021. Français. ⟨NNT : 2021MONTT034⟩. ⟨tel-03431161⟩

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