Abstract

Natural killer cells play a crucial role in the initial defense against bacterial pathogens. The crosstalk between host cells infected with intracellular pathogens and NK cells has been studied intensively, but not much attention has been given to characterize the role of NK cells in the response to extracellular bacterial pathogens such as yersiniae. In this study we used antibody-mediated NK cell depletion to address the importance of this immune cell type in controlling a Y. pseudotuberculosis infection. Analysis of the bacterial counts was used to follow the infection and flow cytometry was performed to characterize the composition and dynamic of immune cells. Depletion of NK cells led to higher bacterial loads within the mesenteric lymph nodes. We further show that in particular CD11b+ CD27+ NK cells which express higher levels of the activation marker CD69 increase within the mesenteric lymph nodes during a Y. pseudotuberculosis infection. Moreover, in response to the activation NK cells secrete higher levels of IFNy, which in turn triggers the production of the proinflammatory cytokine TNFα. These results suggest, that NK cells aid in the clearance of Y. pseudotuberculosis infections mainly by triggering the expression of proinflammatory cytokines manipulating the host immune response.

Highlights

  • The genus Yersinia includes three species, which are well known to cause infections in humans: Yersinia pestis, Y. pseudotuberculosis and Y. enterocolitica

  • It was previously shown by our group that upon infection with Y. pseudotuberculosis YPIII, natural killer (NK) cell numbers in Peyers patches (PPs) and mesenteric lymph nodes (mLNs) increased while a decrease of NK cells occurred in the spleen and blood [23, 24]

  • This finding suggests that NK and/or NKT cells might play a protective role against Y. pseudotuberculosis infection

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Summary

Introduction

The genus Yersinia includes three species, which are well known to cause infections in humans: Yersinia pestis, Y. pseudotuberculosis and Y. enterocolitica. Y. pseudotuberculosis and Y. enterocolitica are enteric pathogens associated with food borne infections resulting in different intestinal diseases such as diarrhea, enteritis and mesenteric lymphadenitis addressed as Yersiniosis [1, 2]. In immunocompromised individuals the inability to control the infection and to limit inflammation can lead to severe sequelae such as erythema nodosum and reactive arthritis [1]. Y. pestis, a close relative of Y. pseudotuberculosis, is transmitted by rodents and infected fleas, and causes severe illness (bubonic and pneumonic plague) and death in humans [3]. All three Yersinia species are characterized by their tropism for lymphatic tissues [4]. After colonization of the gastrointestinal tract by both enteric Yersinia species, the bacteria invade into

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