PMID- 25200028
OWN - NLM
STAT- MEDLINE
DCOM- 20141117
LR  - 20230703
IS  - 1540-9538 (Electronic)
IS  - 0022-1007 (Print)
IS  - 0022-1007 (Linking)
VI  - 211
IP  - 10
DP  - 2014 Sep 22
TI  - Oral-resident natural Th17 cells and gammadelta T cells control opportunistic Candida 
      albicans infections.
PG  - 2075-84
LID - 10.1084/jem.20130877 [doi]
AB  - Oropharyngeal candidiasis (OPC) is an opportunistic fungal infection caused by 
      Candida albicans. OPC is frequent in HIV/AIDS, implicating adaptive immunity. 
      Mice are naive to Candida, yet IL-17 is induced within 24 h of infection, and 
      susceptibility is strongly dependent on IL-17R signaling. We sought to identify 
      the source of IL-17 during the early innate response to candidiasis. We show that 
      innate responses to Candida require an intact TCR, as SCID, IL-7Ralpha(-/-), and 
      Rag1(-/-) mice were susceptible to OPC, and blockade of TCR signaling by 
      cyclosporine induced susceptibility. Using fate-tracking IL-17 reporter mice, we 
      found that IL-17 is produced within 1-2 d by tongue-resident populations of gammadelta T 
      cells and CD3(+)CD4(+)CD44(hi)TCRbeta(+)CCR6(+) natural Th17 (nTh17) cells, but not 
      by TCR-deficient innate lymphoid cells (ILCs) or NK cells. These cells function 
      redundantly, as TCR-beta(-/-) and TCR-delta(-/-) mice were both resistant to OPC. 
      Whereas gammadelta T cells were previously shown to produce IL-17 during dermal 
      candidiasis and are known to mediate host defense at mucosal surfaces, nTh17 
      cells are poorly understood. The oral nTh17 population expanded rapidly after 
      OPC, exhibited high TCR-beta clonal diversity, and was absent in Rag1(-/-), 
      IL-7Ralpha(-/-), and germ-free mice. These findings indicate that nTh17 and gammadelta T 
      cells, but not ILCs, are key mucosal sentinels that control oral pathogens.
CI  - (c) 2014 Conti et al.
FAU - Conti, Heather R
AU  - Conti HR
AD  - Division of Rheumatology and Clinical Immunology, and Division of 
      Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Department 
      of Immunology, and Center for Biological Imaging, University of Pittsburgh, 
      Pittsburgh, PA 15261.
FAU - Peterson, Alanna C
AU  - Peterson AC
AD  - Division of Rheumatology and Clinical Immunology, and Division of 
      Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Department 
      of Immunology, and Center for Biological Imaging, University of Pittsburgh, 
      Pittsburgh, PA 15261.
FAU - Brane, Lucas
AU  - Brane L
AD  - Division of Rheumatology and Clinical Immunology, and Division of 
      Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Department 
      of Immunology, and Center for Biological Imaging, University of Pittsburgh, 
      Pittsburgh, PA 15261.
FAU - Huppler, Anna R
AU  - Huppler AR
AD  - Department of Infectious Diseases, Children's Hospital of Pittsburgh, Pittsburgh, 
      PA 15224.
FAU - Hernandez-Santos, Nydiaris
AU  - Hernandez-Santos N
AD  - Division of Rheumatology and Clinical Immunology, and Division of 
      Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Department 
      of Immunology, and Center for Biological Imaging, University of Pittsburgh, 
      Pittsburgh, PA 15261.
FAU - Whibley, Natasha
AU  - Whibley N
AD  - Division of Rheumatology and Clinical Immunology, and Division of 
      Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Department 
      of Immunology, and Center for Biological Imaging, University of Pittsburgh, 
      Pittsburgh, PA 15261.
FAU - Garg, Abhishek V
AU  - Garg AV
AD  - Division of Rheumatology and Clinical Immunology, and Division of 
      Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Department 
      of Immunology, and Center for Biological Imaging, University of Pittsburgh, 
      Pittsburgh, PA 15261.
FAU - Simpson-Abelson, Michelle R
AU  - Simpson-Abelson MR
AD  - Division of Rheumatology and Clinical Immunology, and Division of 
      Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Department 
      of Immunology, and Center for Biological Imaging, University of Pittsburgh, 
      Pittsburgh, PA 15261.
FAU - Gibson, Gregory A
AU  - Gibson GA
AD  - Division of Rheumatology and Clinical Immunology, and Division of 
      Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Department 
      of Immunology, and Center for Biological Imaging, University of Pittsburgh, 
      Pittsburgh, PA 15261.
FAU - Mamo, Anna J
AU  - Mamo AJ
AD  - Division of Rheumatology and Clinical Immunology, and Division of 
      Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Department 
      of Immunology, and Center for Biological Imaging, University of Pittsburgh, 
      Pittsburgh, PA 15261.
FAU - Osborne, Lisa C
AU  - Osborne LC
AD  - Department of Microbiology, Perelman School of Medicine, University of 
      Pennsylvania, Philadelphia, PA 19104.
FAU - Bishu, Shrinivas
AU  - Bishu S
AD  - Division of Rheumatology and Clinical Immunology, and Division of 
      Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Department 
      of Immunology, and Center for Biological Imaging, University of Pittsburgh, 
      Pittsburgh, PA 15261.
FAU - Ghilardi, Nico
AU  - Ghilardi N
AD  - Department of Immunology, Genentech Inc., South San Francisco, CA 94080.
FAU - Siebenlist, Ulrich
AU  - Siebenlist U
AD  - Laboratory of Immunoregulation, National Institute of Allergy and Infectious 
      Diseases, National Institutes of Health, Bethesda, MD 20852.
FAU - Watkins, Simon C
AU  - Watkins SC
AD  - Division of Rheumatology and Clinical Immunology, and Division of 
      Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Department 
      of Immunology, and Center for Biological Imaging, University of Pittsburgh, 
      Pittsburgh, PA 15261.
FAU - Artis, David
AU  - Artis D
AD  - Department of Microbiology, Perelman School of Medicine, University of 
      Pennsylvania, Philadelphia, PA 19104.
FAU - McGeachy, Mandy J
AU  - McGeachy MJ
AD  - Division of Rheumatology and Clinical Immunology, and Division of 
      Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Department 
      of Immunology, and Center for Biological Imaging, University of Pittsburgh, 
      Pittsburgh, PA 15261 Division of Rheumatology and Clinical Immunology, and 
      Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, 
      Department of Immunology, and Center for Biological Imaging, University of 
      Pittsburgh, Pittsburgh, PA 15261.
FAU - Gaffen, Sarah L
AU  - Gaffen SL
AD  - Division of Rheumatology and Clinical Immunology, and Division of 
      Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Department 
      of Immunology, and Center for Biological Imaging, University of Pittsburgh, 
      Pittsburgh, PA 15261 Division of Rheumatology and Clinical Immunology, and 
      Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, 
      Department of Immunology, and Center for Biological Imaging, University of 
      Pittsburgh, Pittsburgh, PA 15261 sig65@pitt.edu.
LA  - eng
GR  - DE023815/DE/NIDCR NIH HHS/United States
GR  - R37 DE022550/DE/NIDCR NIH HHS/United States
GR  - R01 AI095466/AI/NIAID NIH HHS/United States
GR  - P01 AI106697/AI/NIAID NIH HHS/United States
GR  - AI1110822/AI/NIAID NIH HHS/United States
GR  - U54 GM103529/GM/NIGMS NIH HHS/United States
GR  - DE022550/DE/NIDCR NIH HHS/United States
GR  - T32 DK063922/DK/NIDDK NIH HHS/United States
GR  - F32-AI098243/AI/NIAID NIH HHS/United States
GR  - R01 DE022550/DE/NIDCR NIH HHS/United States
GR  - F32 AI098243/AI/NIAID NIH HHS/United States
GR  - R01 AI107825/AI/NIAID NIH HHS/United States
GR  - F32 DE023293/DE/NIDCR NIH HHS/United States
GR  - R01 DE023815/DE/NIDCR NIH HHS/United States
GR  - AI106697/AI/NIAID NIH HHS/United States
GR  - R56 AI110822/AI/NIAID NIH HHS/United States
GR  - AI107825/AI/NIAID NIH HHS/United States
GR  - R01 AI097333/AI/NIAID NIH HHS/United States
GR  - AI095466/AI/NIAID NIH HHS/United States
GR  - F32-DE023293/DE/NIDCR NIH HHS/United States
GR  - T32-DK063922/DK/NIDDK NIH HHS/United States
GR  - AI097333/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20140908
PL  - United States
TA  - J Exp Med
JT  - The Journal of experimental medicine
JID - 2985109R
RN  - 0 (Il17ra protein, mouse)
RN  - 0 (Interleukin-23)
RN  - 0 (Receptors, Antigen, T-Cell, gamma-delta)
RN  - 0 (Receptors, Interleukin-17)
SB  - IM
MH  - Animals
MH  - Candida albicans/*immunology
MH  - Candidiasis/immunology/*prevention & control
MH  - Flow Cytometry
MH  - Immunity, Innate/*immunology
MH  - Interleukin-23/deficiency
MH  - Mice
MH  - Mice, Knockout
MH  - Microscopy, Confocal
MH  - Mouth/cytology/*immunology/microbiology
MH  - Real-Time Polymerase Chain Reaction
MH  - Receptors, Antigen, T-Cell, gamma-delta/metabolism
MH  - Receptors, Interleukin-17/deficiency/metabolism
MH  - Th17 Cells/*immunology
PMC - PMC4172215
EDAT- 2014/09/10 06:00
MHDA- 2014/11/18 06:00
PMCR- 2015/03/22
CRDT- 2014/09/10 06:00
PHST- 2014/09/10 06:00 [entrez]
PHST- 2014/09/10 06:00 [pubmed]
PHST- 2014/11/18 06:00 [medline]
PHST- 2015/03/22 00:00 [pmc-release]
AID - jem.20130877 [pii]
AID - 20130877 [pii]
AID - 10.1084/jem.20130877 [doi]
PST - ppublish
SO  - J Exp Med. 2014 Sep 22;211(10):2075-84. doi: 10.1084/jem.20130877. Epub 2014 Sep 
      8.