Role of eosinophils in SIV infection

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PROJECT SUMMARY Chronic HIV infection is associated with increased risk of co-morbidities including diabetes mellitus, cardiovascular diseases, neuro-dysfunctions and cancer, due to the state of persistent inflammation and immune dysfunction induced by the virus. Further, HIV causes gut leakage and intestinal inflammation in the gastrointestinal tract of infected patients. Eosinophils are an important innate cell subset that are highly enriched in small and large intestines with gut homeostatic functions, but their role in mucosal viral infections have been mostly overlooked. In our recent publication (Jones et al, 2021; Immunology), we phenotypically characterized different subsets of granulocytes in rhesus macaques and found non-human primate (NHP) eosinophils analogous to human eosinophils and were found enriched in jejunum, suggesting that these tissue-resident eosinophils are well situated and capable of eliciting early antiviral mucosal responses. However, the pro-inflammatory responses of eosinophils- cytotoxicity, cytokine secretion, reactive oxygen species generation can also cause tissue damage. Further, there is a lack of knowledge of potential reprogramming of eosinophils in HIV infection that could contribute to clearance of pathogens and/or pathologic manifestations. In this new exploratory proposal, we will test the role of eosinophils contributing to antiviral responses that lead to viral clearance or pathogenic mechanisms that lead to persistent inflammation in lentivirus infection. Our two specific aims towards this goal are: (1) Determine the relative contribution of eosinophils to lentiviral pathology and control and (2) Evaluate mechanisms of trained immunity in eosinophils upon de novo infection with SIV in rhesus macaques. The outcomes of this proposal will provide first time detailed analysis of an eosinophil depleted immune system in any viral infection and reprogrammed eosinophils ‘trained’ in the context of SIV infection.