Abstract
Dendritic cells (DCs) and NK cells play a crucial role in the first phase of host defense against infections. Group B Streptococcus (GBS) and Streptococcus suis are encapsulated streptococci causing severe systemic inflammation, leading to septicemia and meningitis. Yet, the involvement of NK cells in the innate immune response to encapsulated bacterial infection is poorly characterized. Here, it was observed that these two streptococcal species rapidly induce the release of IFN-γ and that NK cells are the major cell type responsible for this production during the acute phase of the infection. Albeit S. suis capacity to activate NK cells was lower than that of GBS, these cells partially contribute to S. suis systemic infection; mainly through amplification of the inflammatory loop. In contrast, such a role was not observed during GBS systemic infection. IFN-γ release by NK cells required the presence of DCs, which in turn had a synergistic effect on DC cytokine production. These responses were mainly mediated by direct DC-NK cell contact and partially dependent on soluble factors. Though IL-12 and LFA-1 were shown to be critical in S. suis-mediated activation of the DC-NK cell crosstalk, different or redundant molecular pathways modulate DC-NK interactions during GBS infection. The bacterial capsular polysaccharides also differently modulated NK cell activation. Together, these results demonstrated a role of NK cells in the innate immune response against encapsulated streptococcal infections; yet the molecular pathways governing NK activation seem to differ upon the pathogen and should not be generalized when studying bacterial infections.
Highlights
Streptococcus suis and Group B Streptococcus (GBS, or Streptococcus agalactiae) are two encapsulated pathogens that induce similar pathologies, including septicemia and meningitis in animals and/or humans
We focused on the LFA-1 adhesion molecule and on the NKG2D-activating receptor, as these two receptors have been reported to play a role in the dendritic cell (DC)-natural killer (NK) crosstalk or during bacterial infections (Binnerts and van Kooyk, 1999; Guan et al, 2007; Wesselkamper et al, 2008; Jiao et al, 2011; Bouwer et al, 2013)
Despite advances in understanding the pathogenesis of disease caused by encapsulated bacteria, on the interactions between these bacteria and cells of the innate immunity, such as DCs, macrophages and neutrophils, few studies had focused on the importance of NK cells during GBS or S. suis infections
Summary
Streptococcus suis and Group B Streptococcus (GBS, or Streptococcus agalactiae) are two encapsulated pathogens that induce similar pathologies, including septicemia and meningitis in animals and/or humans. S. suis is a major swine pathogen and emerging threat to human health, especially in Asian countries (Gottschalk et al, 2010; Fittipaldi et al, 2012). S. suis is the leading cause of adult meningitis in Vietnam, the second in Thailand and the third in Hong Kong (Gottschalk et al, 2010). Streptococcus Interactions with NK Cells serotypes that have been described, type 2 S. suis is the most virulent for both pigs and humans, and most of the studies have been performed with this serotype. Type 14 S. suis is emerging as a zoonotic agent (Goyette-Desjardins et al, 2014)
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