T cell infiltration into the brain triggers pulmonary dysfunction in murine Cryptococcus-associated IRIS.

Abstract

Cryptococcus-associated immune reconstitution inflammatory syndrome (C-IRIS) is a condition frequently occurring in immunocompromised patients receiving antiretroviral therapy. C-IRIS patients exhibit many critical symptoms, including pulmonary distress, potentially complicating the progression and recovery from this condition. Here, utilizing our previously established mouse model of unmasking C-IRIS (CnH99 preinfection and adoptive transfer of CD4T cells), we demonstrated that pulmonary dysfunction associated with the C-IRIS condition in mice could be attributed to the infiltration of CD4T cells into the brain via the CCL8-CCR5 axis, which triggers the nucleus tractus solitarius (NTS) neuronal damage and neuronal disconnection via upregulated ephrin B3 and semaphorin 6B in CD4T cells. Our findings provide unique insight into the mechanism behind pulmonary dysfunction in C-IRIS and nominate potential therapeutic targets for treatment.