Enteric bacteria induce IFNγ and Granzyme B from human colonic Group 1 Innate Lymphoid Cells

Moriah J. Castleman, Stephanie M. Dillon, Christine Purba, Andrew C. Cogswell, Martin McCarter, Edward Barker, Cara Wilson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Group 1 Innate Lymphoid Cells (which include Natural Killer cells and ILC1s) aid in gut anti-bacterial defense through the production of IFNγ, which is critical for mobilizing protective responses against enteric pathogens. When intestinal epithelial barrier integrity is compromised, commensal bacteria are likely to translocate from the gut lumen into the lamina propria. Few studies have addressed the mechanisms by which commensal bacteria impact the function of gut Group 1 ILCs, especially ILC1s. Utilizing an in vitro human colonic lamina propria mononuclear cell (LPMC) model, we evaluated Group 1 ILC cytokine and cytolytic protein production in response to a panel of enteric Gram-positive and Gram-negative commensal and pathogenic bacteria. IFNγ-production by NK cells and ILC1s was significantly increased after LPMC exposure to Gram-negative commensal or pathogenic bacteria, but not after exposure to the Gram-positive bacteria commensals tested. Stimulation of IFNγ production from Group 1 ILCs was not through direct recognition of bacteria by NK cells or ILC1s, but rather required accessory cells within the LPMC population. Myeloid dendritic cells generated IL-12p70, IL-18, and IL-1β upon exposure to enteric bacteria and these cytokines contributed to Group 1 ILC production of IFNγ. Furthermore, Gram-negative commensal or pathogenic bacteria induced significant expression of Granzyme B in NK cells and ILC1s. Overall, these data demonstrate that some enteric commensal bacteria indirectly induce inflammatory cytokine production and cytolytic protein expression from human colonic Group 1 ILCs, a process which could contribute to inflammation in the setting of microbial translocation.

Original languageEnglish (US)
Article number1667723
JournalGut Microbes
Volume12
Issue number1
DOIs
StatePublished - Nov 9 2020

Keywords

  • Group 1 ILCs
  • IFNγ
  • IL-12p70
  • IL-18
  • IL-1β
  • ILC1
  • NK cells
  • colonic mucosa
  • commensal bacteria
  • human

ASJC Scopus subject areas

  • Microbiology (medical)
  • Gastroenterology
  • Infectious Diseases
  • Microbiology

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