C-type lectin receptor dysregulation in HIV and <i>Mycobacterium tuberculosis</i>co-infection

Abstract Infection with Mycobacterium tuberculosis (Mtb) is a serious and potentially life-threatening condition, especially in people HIV (PWH). According to the WHO, there were 10.6 million new (TB) cases 2021, 700,000 of those among PWH. Macrophages are host cell for both pathogens play an important innate immune role determining outcome disease. C-type lectin receptors (CLR) pattern recognition (PRR) abundantly expressed on macrophage surface that orchestrate response microbial insults. We previously identified galactose-type receptor (MGL) CLR protection against TB. In subsequent studies, we observed suppression MGL tissues HIV-infected decedents human macrophages following vitro infection HIV. THP-1 cells humanized mouse model, observe markedly impairs activation by mycobacteria comparison other CLRs defined roles antimycobacterial immunity including DC-SIGN Dectin 1. further determine TLR2/6 heterodimer, TLR4, TGF-β signaling pathways transcriptional regulation MGL. Importantly, these have pathogenesis Mtb or infections. These findings advance our understanding as part repertoire, well its Mtb/HIV co-infection. NIH R31AI138328, R61AI138328