Regionally compartmentalized resident memory T cells mediate naturally acquired protection against pneumococcal pneumonia

Mucosal Immunology
N Ms SmithJ P Mizgerd

Abstract

As children age, they become less susceptible to the diverse microbes causing pneumonia. These microbes are pathobionts that infect the respiratory tract multiple times during childhood, generating immunological memory. To elucidate mechanisms of such naturally acquired immune protection against pneumonia, we modeled a relevant immunological history in mice by infecting their airways with mismatched serotypes of Streptococcus pneumoniae (pneumococcus). Previous pneumococcal infections provided protection against a heterotypic, highly virulent pneumococcus, as evidenced by reduced bacterial burdens and long-term sterilizing immunity. This protection was diminished by depletion of CD4+ cells prior to the final infection. The resolution of previous pneumococcal infections seeded the lungs with CD4+ resident memory T (TRM) cells, which responded to heterotypic pneumococcus stimulation by producing multiple effector cytokines, particularly interleukin (IL)-17A. Following lobar pneumonias, IL-17-producing CD4+ TRM cells were confined to the previously infected lobe, rather than dispersed throughout the lower respiratory tract. Importantly, pneumonia protection also was confined to that immunologically experienced lobe. Thus regionall...Continue Reading

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Citations

May 17, 2018·Physiological Reviews·Lee J QuintonJoseph P Mizgerd
Mar 17, 2018·American Journal of Respiratory and Critical Care Medicine·Charles S Dela CruzJoseph P Mizgerd
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Datasets Mentioned

BETA
GM-CSF

Methods Mentioned

BETA
bronchoalveolar lavage
Bronchoalveolar
enzyme-linked immunosorbent assay
ELISA
flow cytometry

Software Mentioned

FlowJo
GraphPad
GraphPad Prism

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