PMID- 27783671
OWN - NLM
STAT- MEDLINE
DCOM- 20170519
LR  - 20210109
IS  - 1553-7374 (Electronic)
IS  - 1553-7366 (Print)
IS  - 1553-7366 (Linking)
VI  - 12
IP  - 10
DP  - 2016 Oct
TI  - NK-CD11c+ Cell Crosstalk in Diabetes Enhances IL-6-Mediated Inflammation during 
      Mycobacterium tuberculosis Infection.
PG  - e1005972
LID - 10.1371/journal.ppat.1005972 [doi]
LID - e1005972
AB  - 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.
FAU - Cheekatla, Satyanarayana Swamy
AU  - Cheekatla SS
AD  - Department of Pulmonary Immunology, Center for Biomedical Research, University of 
      Texas Health Science Center at Tyler, Tyler, Texas, United States of America.
FAU - Tripathi, Deepak
AU  - Tripathi D
AD  - Department of Pulmonary Immunology, Center for Biomedical Research, University of 
      Texas Health Science Center at Tyler, Tyler, Texas, United States of America.
FAU - Venkatasubramanian, Sambasivan
AU  - Venkatasubramanian S
AD  - Department of Pulmonary Immunology, Center for Biomedical Research, University of 
      Texas Health Science Center at Tyler, Tyler, Texas, United States of America.
FAU - Nathella, Pavan Kumar
AU  - Nathella PK
AD  - National Institutes of Health, International Center for Excellence in Research, 
      Chennai, India.
FAU - Paidipally, Padmaja
AU  - Paidipally P
AD  - Department of Pulmonary Immunology, Center for Biomedical Research, University of 
      Texas Health Science Center at Tyler, Tyler, Texas, United States of America.
FAU - Ishibashi, Munenori
AU  - Ishibashi M
AD  - Department of Cellular and Molecular Biology, Center for Biomedical Research, 
      University of Texas Health Science Center at Tyler, Tyler, Texas, United States 
      of America.
FAU - Welch, Elwyn
AU  - Welch E
AD  - Department of Pulmonary Immunology, Center for Biomedical Research, University of 
      Texas Health Science Center at Tyler, Tyler, Texas, United States of America.
FAU - Tvinnereim, Amy R
AU  - Tvinnereim AR
AD  - Department of Pulmonary Immunology, Center for Biomedical Research, University of 
      Texas Health Science Center at Tyler, Tyler, Texas, United States of America.
FAU - Ikebe, Mitsuo
AU  - Ikebe M
AD  - Department of Cellular and Molecular Biology, Center for Biomedical Research, 
      University of Texas Health Science Center at Tyler, Tyler, Texas, United States 
      of America.
FAU - Valluri, Vijaya Lakshmi
AU  - Valluri VL
AD  - Blue Peter Research Center, LEPRA Society, Cherlapally, Hyderabad, India.
FAU - Babu, Subash
AU  - Babu S
AD  - National Institutes of Health, International Center for Excellence in Research, 
      Chennai, India.
FAU - Kornfeld, Hardy
AU  - Kornfeld H
AD  - Department of Medicine, University of Massachusetts Medical School, Worcester, 
      MA, United States of America.
FAU - Vankayalapati, Ramakrishna
AU  - Vankayalapati R
AD  - Department of Pulmonary Immunology, Center for Biomedical Research, University of 
      Texas Health Science Center at Tyler, Tyler, Texas, United States of America.
LA  - eng
GR  - R01 HL081149/HL/NHLBI NIH HHS/United States
GR  - R01 HL127384/HL/NHLBI NIH HHS/United States
PT  - Journal Article
DEP - 20161026
PL  - United States
TA  - PLoS Pathog
JT  - PLoS pathogens
JID - 101238921
RN  - 0 (Interleukin-6)
SB  - IM
MH  - Animals
MH  - Diabetes Mellitus, Experimental/*complications/*immunology
MH  - Diabetes Mellitus, Type 2/complications/immunology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Humans
MH  - Immunohistochemistry
MH  - Inflammation/immunology
MH  - Interleukin-6/immunology
MH  - Killer Cells, Natural/*immunology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Microscopy, Confocal
MH  - Mycobacterium tuberculosis
MH  - Real-Time Polymerase Chain Reaction
MH  - Receptor Cross-Talk/immunology
MH  - Tuberculosis/*complications/*immunology
PMC - PMC5082658
COIS- The authors have declared that no competing interests exist.
EDAT- 2016/10/27 06:00
MHDA- 2017/05/20 06:00
PMCR- 2016/10/26
CRDT- 2016/10/27 06:00
PHST- 2016/02/01 00:00 [received]
PHST- 2016/10/03 00:00 [accepted]
PHST- 2016/10/27 06:00 [pubmed]
PHST- 2017/05/20 06:00 [medline]
PHST- 2016/10/27 06:00 [entrez]
PHST- 2016/10/26 00:00 [pmc-release]
AID - PPATHOGENS-D-16-00232 [pii]
AID - 10.1371/journal.ppat.1005972 [doi]
PST - epublish
SO  - PLoS Pathog. 2016 Oct 26;12(10):e1005972. doi: 10.1371/journal.ppat.1005972. 
      eCollection 2016 Oct.