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Mucosal Immunol. 2018 Jan;11(1):220-235. doi: 10.1038/mi.2017.43. Epub 2017 May 17.

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

Author information

1
Pulmonary Center, Boston University School of Medicine, Boston Massachusetts, USA.
2
Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston Massachusetts, USA.
3
Department of Microbiology, Boston University School of Medicine, Boston Massachusetts, USA.
4
Second Department of Internal Medicine, Nagasaki University Hospital, Nagasaki, Japan.
5
Department of Clinical Research Center, National Hospital Organization Nagasaki Medical Center, Omura, Japan.
6
Division of Infectious Diseases, Boston Children's Hospital, Boston Massachusetts, USA.
7
Department of Medicine, Arthritis Center/Rheumatology Section, Boston University School of Medicine, Boston Massachusetts, USA.
8
Department of Medicine, Boston University School of Medicine, Boston Massachusetts, USA.
9
Department of Biochemistry, Boston University School of Medicine, Boston Massachusetts, USA.

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 regionally localized memory cells provide superior local tissue protection to that mediated by systemic or central memory immune defenses. We conclude that respiratory bacterial infections elicit CD4+ TRM cells that fill a local niche to optimize heterotypic protection of the affected tissue, preventing pneumonia.

PMID:
28513594
PMCID:
PMC5693795
DOI:
10.1038/mi.2017.43
[Indexed for MEDLINE]
Free PMC Article

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