title: Phagocytosis via complement or Fc-gamma receptors is compromised in monocytes from type 2 diabetes patients with chronic hyperglycemia.
abstract: Type 2 diabetes patients (DM2) have a higher risk of tuberculosis (TB) that may be attributed to functional defects in their mononuclear phagocytes given the critical role of these cells in Mycobacterium tuberculosis containment. Our previous findings suggest that monocytes from DM2 have reduced association with serum-opsonized M. tuberculosis. To determine if this alteration is due to defects in phagocytosis via complement or Fc-gamma receptors (FcγRs), in this study we evaluated the uptake of sheep red blood cells coated with IgG or complement, respectively, by monocytes from individuals with and without DM2. We found that chronic hyperglycemia was significantly associated with reduced phagocytosis via either receptor by univariable and multivariable analyses. This defect was independent of host serum opsonins and flow cytometry data indicated this was not attributed to reduced expression of these phagocytic receptors on DM2 monocytes. The positive correlation between both pathways (R = 0.64; p = 0.003) indicate that monocytes from individuals with chronic hyperglycemia have a defect in the two predominant phagocytic pathways of these cells. Given that phagocytosis is linked to activation of effector mechanisms for bacterial killing, it is likely that this defect is one factor contributing to the higher susceptibility of DM2 patients to pathogens like M. tuberculosis.
authors.affiliation: Division of Epidemiology, UTHealth Houston, School of Public Health at Brownsville, Brownsville, Texas, United States of America.
authors.forename: Blanca I
authors.initials: BI
authors.lastname: Restrepo
authors.affiliation: Joslin Diabetes Center-Doctors Hospital at Renaissance, Edinburg, Texas, United States of America.
authors.forename: Marcel
authors.initials: M
authors.lastname: Twahirwa
authors.affiliation: Division of Clinical and Translational Sciences, Department of Internal Medicine, Medical School, University of Texas Health Science Center at Houston, Houston, Texas, United States of America.
authors.forename: Mohammad H
authors.initials: MH
authors.lastname: Rahbar
authors.affiliation: Center for Microbial Interface Biology and Department of Microbial Infection and Immunity, The Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Larry S
authors.initials: LS
authors.lastname: Schlesinger
mesh_terms: D000328:Adult; D000818:Animals; D002908:Chronic Disease; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000276:immunology* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D005453:Fluorescence; D006801:Humans; D006943:Hyperglycemia / Q000150:complications* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D010587:Phagocytosis; D010641:Phenotype; D011951:Receptors, Complement / Q000378:metabolism*; D017452:Receptors, IgG / Q000378:metabolism*; D012756:Sheep
chemical_list: D011951:Receptors, Complement; D017452:Receptors, IgG