title: NK-CD11c+ Cell Crosstalk in Diabetes Enhances IL-6-Mediated Inflammation during Mycobacterium tuberculosis Infection.
abstract: In this study, we developed a mouse model of type 2 diabetes mellitus (T2DM) using streptozotocin and nicotinamide and identified factors that increase susceptibility of T2DM mice to infection by Mycobacterium tuberculosis (Mtb). All Mtb-infected T2DM mice and 40% of uninfected T2DM mice died within 10 months, whereas all control mice survived. In Mtb-infected mice, T2DM increased the bacterial burden and pro- and anti-inflammatory cytokine and chemokine production in the lungs relative to those in uninfected T2DM mice and infected control mice. Levels of IL-6 also increased. Anti-IL-6 monoclonal antibody treatment of Mtb-infected acute- and chronic-T2DM mice increased survival (to 100%) and reduced pro- and anti-inflammatory cytokine expression. CD11c+ cells were the major source of IL-6 in Mtb-infected T2DM mice. Pulmonary natural killer (NK) cells in Mtb-infected T2DM mice further increased IL-6 production by autologous CD11c+ cells through their activating receptors. Anti-NK1.1 antibody treatment of Mtb-infected acute-T2DM mice increased survival and reduced pro- and anti-inflammatory cytokine expression. Furthermore, IL-6 increased inflammatory cytokine production by T lymphocytes in pulmonary tuberculosis patients with T2DM. Overall, the results suggest that NK-CD11c+ cell interactions increase IL-6 production, which in turn drives the pathological immune response and mortality associated with Mtb infection in diabetic mice.
authors: Department of Pulmonary Immunology, Center for Biomedical Research, University of Texas Health Science Center at Tyler, Tyler, Texas, United States of America.
authors: Satyanarayana Swamy
authors: SS
authors: Cheekatla
authors: Department of Pulmonary Immunology, Center for Biomedical Research, University of Texas Health Science Center at Tyler, Tyler, Texas, United States of America.
authors: Deepak
authors: D
authors: Tripathi
authors: Department of Pulmonary Immunology, Center for Biomedical Research, University of Texas Health Science Center at Tyler, Tyler, Texas, United States of America.
authors: Sambasivan
authors: S
authors: Venkatasubramanian
authors: National Institutes of Health, International Center for Excellence in Research, Chennai, India.
authors: Pavan Kumar
authors: PK
authors: Nathella
authors: Department of Pulmonary Immunology, Center for Biomedical Research, University of Texas Health Science Center at Tyler, Tyler, Texas, United States of America.
authors: Padmaja
authors: P
authors: Paidipally
authors: Department of Cellular and Molecular Biology, Center for Biomedical Research, University of Texas Health Science Center at Tyler, Tyler, Texas, United States of America.
authors: Munenori
authors: M
authors: Ishibashi
authors: Department of Pulmonary Immunology, Center for Biomedical Research, University of Texas Health Science Center at Tyler, Tyler, Texas, United States of America.
authors: Elwyn
authors: E
authors: Welch
authors: Department of Pulmonary Immunology, Center for Biomedical Research, University of Texas Health Science Center at Tyler, Tyler, Texas, United States of America.
authors: Amy R
authors: AR
authors: Tvinnereim
authors: Department of Cellular and Molecular Biology, Center for Biomedical Research, University of Texas Health Science Center at Tyler, Tyler, Texas, United States of America.
authors: Mitsuo
authors: M
authors: Ikebe
authors: Blue Peter Research Center, LEPRA Society, Cherlapally, Hyderabad, India.
authors: Vijaya Lakshmi
authors: VL
authors: Valluri
authors: National Institutes of Health, International Center for Excellence in Research, Chennai, India.
authors: Subash
authors: S
authors: Babu
authors: Department of Medicine, University of Massachusetts Medical School, Worcester, MA, United States of America.
authors: Hardy
authors: H
authors: Kornfeld
authors: Department of Pulmonary Immunology, Center for Biomedical Research, University of Texas Health Science Center at Tyler, Tyler, Texas, United States of America.
authors: Ramakrishna
authors: R
authors: Vankayalapati
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000276:immunology*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D009169:Mycobacterium tuberculosis; D060888:Real-Time Polymerase Chain Reaction; D020239:Receptor Cross-Talk / Q000276:immunology; D014376:Tuberculosis / Q000150:complications* / Q000276:immunology*
chemical_list: D015850:Interleukin-6