The gut microbiome, mucosal immunity and disease pathogenesis in humans with HIV or idiopathic CD4 lymphocytopenia and in non-human primates with SIV

Chronic activation of the immune system is a hallmark of progressive HIV infection in humans as well as SIV infection in Asian macaque non-human primates. While the etiology of such persistent immune activation is incompletely understood, compromised mucosal barrier function and increased translocation of immunostimulatory microbial products from the gut lumen into the systemic circulation have been implicated in this process. Of note, elements of this pathologic process persist despite viral suppression during antiretroviral therapy (ART).
The research described in this thesis is focused on the assessment of the gut microbiota and mucosal immunity to better understand their contribution to disease pathogenesis and progression during SIV infection of non-human primates, HIV infection in humans, and idiopathic CD4⁺ lymphocytopenia (ICL) in humans, a syndrome defined by low CD4⁺ T cell count (<300/μL) and an increased susceptibility to opportunistic infections but without evidence of systemic inflammation. Furthermore, the thesis includes the investigation of a number of novel therapeutic approaches, given in addition to ART, in order to enhance gut mucosa reconstitution, reduce microbial translocation and downregulate key pathways of inflammation.