Macrophages and neutrophils in lymph node granulomas from Mycobacterium tuberculosis-infected macaques have immunoregulatory phenotypes

Newswise — Tuberculosis (TB) is caused by infection with the Mycobacterium tuberculosis (Mtb). Lung granulomas are the defining pathologic feature of TB but Mtb can infect other organs, including lymph nodes, and causes granulomas to form in these sites. Lymph node granulomas have received less attention than lung granulomas but granulomas in these organs are sites of bacterial persistence and have implications for TB progression. Macrophage subsets and neutrophils in lymph node granulomas have not been extensively studied but the biology of these cells may yield clues that underlie the pathobiology of lymph node infection. Our objective was to describe expression of functional markers and cytokine expression by macrophage subsets and neutrophils in lymph node granulomas and to compare these myeloid cells in lymph node and lung granulomas. We used thoracic lymph node and lung granulomas from cynomolgus macaques, a nonhuman primate that experiences human-like TB pathology and course of disease, to do this work. We found that lymph node epithelioid macrophages were distinct from lymph node dendritic cells but resembled epithelioid macrophages in lung granulomas suggesting these cells share a common progenitor or exposure to common stimuli leads to a phenotypic convergence in different tissues. Macrophages expressed pro- and anti-inflammatory cytokines including type 1 interferon, a cytokine family associated with exacerbated TB. Neutrophils were present in low numbers in non-granulomatous lymph node regions but were selectively recruited to granulomas. Our data suggest that macrophages and neutrophils in lymph node granulomas have immunoregulatory properties that may contribute to local and systemic outcomes in Mtb infection.