Advertisement

 

 

NK-CD11c+ Cell Crosstalk in Diabetes Enhances IL-6-Mediated Inflammation during Mycobacterium tuberculosis Infection.

NK-CD11c+ Cell Crosstalk in Diabetes Enhances IL-6-Mediated Inflammation during Mycobacterium tuberculosis Infection.
Author Information (click to view)

Cheekatla SS, Tripathi D, Venkatasubramanian S, Nathella PK, Paidipally P, Ishibashi M, Welch E, Tvinnereim AR, Ikebe M, Valluri VL, Babu S, Kornfeld H, Vankayalapati R,


Cheekatla SS, Tripathi D, Venkatasubramanian S, Nathella PK, Paidipally P, Ishibashi M, Welch E, Tvinnereim AR, Ikebe M, Valluri VL, Babu S, Kornfeld H, Vankayalapati R, (click to view)

Cheekatla SS, Tripathi D, Venkatasubramanian S, Nathella PK, Paidipally P, Ishibashi M, Welch E, Tvinnereim AR, Ikebe M, Valluri VL, Babu S, Kornfeld H, Vankayalapati R,

Advertisement
Share on FacebookTweet about this on TwitterShare on LinkedIn

PLoS pathogens 2016 Oct 2612(10) e1005972 doi 10.1371/journal.ppat.1005972
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.

Submit a Comment

Your email address will not be published. Required fields are marked *

five − 1 =

[ HIDE/SHOW ]