UC Davis

Mycobacterium avium subspecies hominissuis (MAH) is an opportunistic pathogen that is one of the most globally common etiological agents of human pulmonary nontuberculous mycobacterial infection. Solute Carrier Family 11 Member 1 (SLC11A1) activity within the macrophage mediates antimicrobial activity against MAH and other intracellular pathogens, and abrogation of protein functionality caused by genetic polymorphisms renders humans and mice more susceptible to these infections. While former studies suggest that SLC11A1 confers a protective role during pulmonary MAH infection, no studies have demonstrated this explicitly in an in vivo respiratory infection model in congenic mouse strains with genetic variation only at the Slc11a1 locus on Mouse Chromosome 1. In this work, we infected WT C57BL/6J (susceptible) and congenic Slc11a1G169 C57BL/6J (resistant) mice intranasally with a smooth opaque MAH. From blinded histopathology of lung tissue, we found that Slc11a1G169 C57BL/6J have a trend toward earlier onset pulmonary inflammation and a non-progressive inflammatory pathology compared to WT C57BL/6J lung tissue. CFU enumeration revealed transgenic Slc11a1G169 C57BL/6J had significantly fewer CFUs in lung tissue than WT C57BL/6J infected mice during chronic infection, and that this burden was under bacteriostatic control. Overall, this study revealed that early innate SLC11A1 activity in phagocytes has long-term protective effects appreciable during chronic disease. Due to inconclusive results from ex vivo neutrophil bactericidal infection assays within this study, we cannot distinguish whether neutrophils expressing Slc11a1, in addition to macrophages, also contribute to the in vivo pulmonary resistance phenotype observed.