Goblet cell associated antigen passages are inhibited during Salmonella typhimur/cium infection to prevent pathogen dissemination and limit responses to dietary antigens article

Devesha H. Kulkarni, Keely G. McDonald, Kathryn A. Knoop, Jenny K. Gustafsson, Konrad M. Kozlowski, David A. Hunstad, Mark J. Miller, Rodney D. Newberry

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Dietary antigen acquisition by lamina propria (LP) dendritic cells (DCs) is crucial to induce oral tolerance and maintain homeostasis. However, encountering innocuous antigens during infection can lead to inflammatory responses, suggesting processes may limit steady-state luminal antigen capture during infection. We observed that goblet cell (GC) associated antigen passages (GAPs), a steady-state pathway delivering luminal antigens to LP-DCs, are inhibited during Salmonella infection. GAP inhibition was mediated by IL-1β. Infection abrogated luminal antigen delivery and antigen-specific T cell proliferation in the mesenteric lymph node (MLN). Antigen-specific T cell proliferation to dietary antigen was restored by overriding GAP suppression; however, this did not restore regulatory T cell induction, but induced inflammatory T cell responses. Salmonella translocation to the MLN required GCs and correlated with GAPs. Genetic manipulations overriding GAP suppression, or antibiotics inducing colonic GAPs, but not antibiotics that do not, increased dissemination and worsened outcomes independent of luminal pathogen burden. Thus, steady-state sampling pathways are suppressed during infection to prevent responses to dietary antigens, limit pathogen entry, and lessen the disease. Moreover, antibiotics may worsen Salmonella infection by means beyond blunting gut microbiota colonization resistance, providing new insight into how precedent antibiotic use aggravates enteric infection.

Original languageEnglish (US)
Pages (from-to)1103-1113
Number of pages11
JournalMucosal Immunology
Volume11
Issue number4
DOIs
StatePublished - Jul 1 2018

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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