RespiratoryFrancisella tularensisLive Vaccine Strain Infection Induces Th17 Cells and Prostaglandin E₂, Which Inhibits Generation of Gamma Interferon-Positive T Cells

Abstract

Two key routes of Francisella tularensis infection are through the skin and airway. We wished to understand how the route of inoculation influenced the primary acute adaptive immune response. We show that an intranasal inoculation of the F. tularensis live vaccine strain (LVS) with a 1,000-fold-smaller dose than an intradermal dose results in similar growth kinetics and peak bacterial burdens. In spite of similar bacterial burdens, we demonstrate a difference in the quality, magnitude, and kinetics of the primary acute T-cell response depending on the route of inoculation. Further, we show that prostaglandin E 2 secretion in the lung is responsible for the difference in the gamma interferon (IFN-␥)

Lung CD4−CD8− Double-Negative T Cells Are Prominent Producers of IL-17A and IFN-γ during Primary Respiratory Murine Infection with Francisella tularensis Live Vaccine Strain

“…In this study, we observed that CD4 + T cells produced IL-17A during LVS i.n. infection in numbers that were previously reported [∼10 4 IL-17A + CD4 + T cells/lung; Woolard et al (19)], but we further demonstrate that an additional IL-17A-producing T cell subset, DN T cells, was present in even higher numbers during the peak of LVS i.n. infection (Fig.…”

“…Indeed, the DN T cells observed during LVS infection appear to be phenotypically most similar to an MHC class I-restricted CD4 2 CD8 2 NK1.1 2 DN T cell subset that was identified in a murine allograft rejection model (18,26). Previous studies by Woolard et al (19) following primary sublethal i.d. and i.n.…”

“…Although previous studies reported T cell production of IL-17A during primary i.n. LVS infection (19,27), only conventional CD4, CD8, and gd T cell subsets were examined. In this study, we observed that CD4 + T cells produced IL-17A during LVS i.n.…”

Th17 Cells Are the Dominant T Cell Subtype Primed by Shigella flexneri Mediating Protective Immunity

“…Indeed, the priming of Ag-specific Th17 cells and/or Ag-induced IL-17A production of isolated effector cells has been reported for many pathogens, including intra-and extracellular bacteria, fungi, viruses and parasites, but in most cases the Th17/IL-17A response does not exceed the Th1/IFN-g response (22)(23)(24)(25)(32)(33)(34). It has been suggested that intestinal Citrobacter rodentium and pulmonary Bordetella bronchiseptica infections induce a dominant Th17 cell response, but this has been observed after nonspecific restimulation with PMA/ionomycin (35) or the cellular source of IL-17A has not been defined (36).…”

“…However, several studies suggest that in the acute phase of infection these cytokines are predominately produced by non-T cells, innate-like gd T cells, or nonspecific ab T cells (18)(19)(20)(21). The priming of pathogen-specific Th17 has been demonstrated (22)(23)(24)(25), however, long-term maintenance and the function of Th17 cells in secondary immune responses to pathogens remain poorly understood. We demonstrate in this study that S. flexneri induces a predominant Th17 response, whereas Th1 cells that are only weakly primed and Th2 cells that are undetectable like Shigella-specific CD8 + T cells.…”