TY - JOUR
T1 - IL-10 restrains il-17 to limit lung pathology characteristics following pulmonary infection with francisella tularensis live vaccine strain
AU - Slight, Samantha R.
AU - Monin, Leticia
AU - Gopal, Radha
AU - Avery, Lyndsay
AU - Davis, Marci
AU - Cleveland, Hillary
AU - Oury, Tim D.
AU - Rangel-Moreno, Javier
AU - Khader, Shabaana A.
N1 - Funding Information:
Supported by NIH grants HL105427 (S.A.K.), T32 AI065380-08 (S.R.S.), and U19 AI91036 (J.R.-M.); Children’s Hospital of Pittsburgh Research Advisory Committee, Children’s Hospital of Pittsburgh, University of Pittsburgh Medical Center Health System grants (L.M. and S.R.S.); and Department of Medicine, University of Rochester, funds (J.R.-M.).
PY - 2013/11
Y1 - 2013/11
N2 - IL-10 production during intracellular bacterial infections is generally thought to be detrimental because of its role in suppressing protective T-helper cell 1 (Th1) responses. Francisella tularensis is a facultative intracellular bacterium that activates both Th1 and Th17 protective immune responses. Herein, we report that IL-10-deficient mice (Il10-/-), despite having increased Th1 and Th17 responses, exhibit increased mortality after pulmonary infection with F. tularensis live vaccine strain. We demonstrate that the increased mortality observed in Il10-/--infected mice is due to exacerbated IL-17 production that causes increased neutrophil recruitment and associated lung pathology. Thus, although IL-17 is required for protective immunity against pulmonary infection with F. tularensis live vaccine strain, its production is tightly regulated by IL-10 to generate efficient induction of protective immunity without mediating pathology. These data suggest a critical role for IL-10 in maintaining the delicate balance between host immunity and pathology during pulmonary infection with F. tularensis live vaccine strain.
AB - IL-10 production during intracellular bacterial infections is generally thought to be detrimental because of its role in suppressing protective T-helper cell 1 (Th1) responses. Francisella tularensis is a facultative intracellular bacterium that activates both Th1 and Th17 protective immune responses. Herein, we report that IL-10-deficient mice (Il10-/-), despite having increased Th1 and Th17 responses, exhibit increased mortality after pulmonary infection with F. tularensis live vaccine strain. We demonstrate that the increased mortality observed in Il10-/--infected mice is due to exacerbated IL-17 production that causes increased neutrophil recruitment and associated lung pathology. Thus, although IL-17 is required for protective immunity against pulmonary infection with F. tularensis live vaccine strain, its production is tightly regulated by IL-10 to generate efficient induction of protective immunity without mediating pathology. These data suggest a critical role for IL-10 in maintaining the delicate balance between host immunity and pathology during pulmonary infection with F. tularensis live vaccine strain.
UR - http://www.scopus.com/inward/record.url?scp=84886708386&partnerID=8YFLogxK
U2 - 10.1016/j.ajpath.2013.07.008
DO - 10.1016/j.ajpath.2013.07.008
M3 - Article
C2 - 24007881
AN - SCOPUS:84886708386
SN - 0002-9440
VL - 183
SP - 1397
EP - 1404
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 5
ER -