CCR7 Deficiency Allows Accelerated Clearance of Chlamydia from the Female Reproductive Tract

J Immunol. 2017 Oct 1;199(7):2547-2554. doi: 10.4049/jimmunol.1601314. Epub 2017 Aug 11.

Abstract

Immune mechanisms responsible for pathogen clearance from the female reproductive tract (FRT) are incompletely defined; in particular, the contribution of lymphocyte trafficking to this process is unclear. CCR7-deficient mice have profoundly altered lymphocyte recirculation and display ectopic formation of lymphocyte aggregates within mucosal nonlymphoid tissues, including the FRT. In this study, we investigated how altered lymphocyte distribution in CCR7-deficient mice would affect host responses to Chlamydia muridarum within the reproductive tract. As expected, CCR7-deficient mice exhibited reduced lymphocyte trafficking to lymph nodes and a corresponding increase in T cell populations within the FRT. After intravaginal infection with Chlamydia, CCR7-deficient mice displayed markedly reduced Ag-specific CD4 T cell responses within the local draining iliac lymph nodes, yet robust Th1 and Th17 responses were prominent in the FRT. In addition, Chlamydia-specific Ab responses were dysregulated in CCR7-deficient mice, displaying an unexpected increase in the systemic IgA responses. Importantly, prominent mucosal immune responses in CCR7-deficient mice increased the efficiency of bacteria clearance from the FRT while reducing tissue-associated inflammation and pathology. Thus, increased numbers of lymphocytes within the FRT result in pathogen clearance with reduced immune-mediated pathology.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibodies, Bacterial / biosynthesis
  • Antibodies, Bacterial / blood
  • CD4-Positive T-Lymphocytes / immunology
  • Cell Movement
  • Chlamydia Infections / immunology*
  • Chlamydia Infections / microbiology*
  • Chlamydia muridarum / immunology*
  • Chlamydia muridarum / isolation & purification
  • Female
  • Immunoglobulin A / blood
  • Inflammation / microbiology
  • Lymph Nodes / immunology
  • Mice
  • Mice, Knockout
  • Receptors, CCR7 / deficiency
  • Receptors, CCR7 / genetics
  • Receptors, CCR7 / immunology*
  • Reproductive Tract Infections / immunology*
  • Reproductive Tract Infections / microbiology*
  • Th1 Cells / immunology
  • Th17 Cells / immunology

Substances

  • Antibodies, Bacterial
  • Ccr7 protein, mouse
  • Immunoglobulin A
  • Receptors, CCR7