Neutrophil responses to acute Mycobacterium tuberculosis infection in non-human primates

Abstract

Abstract In human and animal models of Mycobacterium tuberculosis (Mtb) infection, neutrophil involvement is associated with severe active disease and increased tissue pathology in tuberculosis (TB). Transcriptomic analyses of human and non-human primate peripheral blood has identified distinct transcriptional signatures, especially during early stages of infection, that link neutrophils and active disease but the biology of peripheral blood neutrophils in TB remains poorly understood. This study is aimed at understanding neutrophil behavior during early stages of Mtb infection using the non-human primate model of TB infection. To accomplish this, we examined cytokine production, secretion, and gene transcription in cynomolgus macaque peripheral blood neutrophils early after Mtb infection. We found that peripheral blood neutrophils could secrete a surprising range of cytokines in response to mycobacterial stimulation, and in a longitudinal analyses, cytokine expression was upregulated between 3-5 weeks post Mtb infection. Studies on neutrophil transcriptional responses to Mtb were performed to identify changes induced by mycobacterial antigens. These results suggest that changes in host biology during early disease modify peripheral blood neutrophil responses to mycobacteria.