HIV-1 promotes neutrophil infiltration and lung damage in humanized mice co-infected with Mycobacterium tuberculosis (HUM1P.266)

Abstract

Abstract Co-infection with human immunodeficiency virus (HIV) and Mycobacterium tuberculosis (Mtb) promotes aggressive disease through mechanisms that are poorly understood. A recent study suggests an association between peripheral blood neutrophil count and Mtb load in the sputum of human subjects with HIV co-infection. We used our humanized BLT mouse (HuMouse) model of HIV/Mtb co-infection as an investigative tool to study the role of neutrophils in co-infection pathobiology. Humanized mice were infected intravenously with HIV-1 for 3 weeks and then co-infected intranasally with Mtb. Compared to HuMice with Mtb or HIV mono-infections, increased neutrophil numbers were observed in the lungs of co-infected animals, as determined by detection of myeloperoxidase using immunohistochemistry. Consistent with the role of neutrophils to promote immune-mediated pathology in TB disease, greater tissue necrosis and increased mycobacterial burden was observed in the lungs of co-infected animals. In support of these findings, an increased pulmonary production of cytokines and chemokines associated with neutrophil recruitment including IL-8, CXCL5, fractalkine, and IL-17 were also observed in co-infected animals. These studies identify mechanisms for immune-mediated pathology due to HIV/Mtb co-infection that can be targeted to restore immune balance in the lung and complement antimycobacterials.