Influence of chronic hyperglycemia on innate immune response in pathophysiology of pulmonary tuberculosis 2228

Description Alteration in host innate immune responses in diabetes mellitus may lead to development of tuberculosis. Study participants were recruited as type 2 DM patients with or without pulmonary TB (PTB+DM and DM respectively), only PTB, and healthy controls. PMNs and PBMCs were isolated from peripheral blood. MdMs were cultured using GM-CSF. Cell counts and surface marker expression were studied by flowcytometry. Phagocytosis was studied using fluorescent-labelled M.tb. ROS and NO production were assessed using DCFDA and Griess reaction respectively. Bacterial clearance was studied by CFU assay. Reduced phagocytic ability of both PMNs and macrophages was seen under diabetic milieu. Despite neutrophilia, alteration in neutrophil migration along with an exhausted neutrophil phenotype was seen, a plausible reason for the decreased phagocytic capacity observed under diabetic milieu. Macrophages showed altered surface expression of various pathogen recognition receptors along with deranged ROS and NO levels and reduced bacterial clearance capacity suggesting alteration in macrophage effector function under chronic hyperglycemic conditions. Additionally, these innate immune dysfunctions were positively correlated with glycated hemoglobin levels. To conclude, diabetic milieu induces altered phenotypes of innate immune cells resulting in dysregulated effector immune responses against M.tb leading to inefficient clearing of infection at an early stage and a consequent immune pathology. Funding Sources SERB, Dept of Science and Technology, India Topic Categories Innate Immune Responses and Host Defense: Cellular Mechanisms (INC)