The innate immune response elicited by Group A Streptococcus is highly variable among clinical isolates and correlates with the emm type.

Márcia Dinis,Céline Plainvert,Agnès Fouet,Pavel Kovarik,Magalie Longo,Claire Poyart

doi:10.1371/journal.pone.0101464

Abstract

Group A Streptococcus (GAS) infections remain a significant health care problem due to high morbidity and mortality associated with GAS diseases, along with their increasing worldwide prevalence. Macrophages play a key role in the control and clearance of GAS infections. Moreover, pro-inflammatory cytokines production and GAS persistence and invasion are related. In this study we investigated the correlation between the GAS clinical isolates genotypes, their known clinical history, and their ability to modulate innate immune response. We constituted a collection of 40 independent GAS isolates representative of the emm types currently prevalent in France and responsible for invasive (57.5%) and non-invasive (42.5%) clinical manifestations. We tested phagocytosis and survival in mouse bone marrow-derived macrophages and quantified the pro-inflammatory mediators (IL-6, TNF-α) and type I interferon (INF-β) production. Invasive emm89 isolates were more phagocytosed than their non-invasive counterparts, and emm89 isolates more than the other isolates. Regarding the survival, differences were observed depending on the isolate emm type, but not between invasive and non-invasive isolates within the same emm type. The level of inflammatory mediators produced was also emm type-dependent and mostly invasiveness status independent. Isolates of the emm1 type were able to induce the highest levels of both pro-inflammatory cytokines, whereas emm89 isolates induced the earliest production of IFN-β. Finally, even within emm types, there was a variability of the innate immune responses induced, but survival and inflammatory mediator production were not linked.

Highlights

Group A Streptococcus (GAS, Streptococcus pyogenes) is among the most ubiquitous and versatile human bacterial pathogen with major healthcare and economic impacts [1,2]
Our findings demonstrate that innate immune response elicited by Group A Streptococcus is highly variable among clinical isolates and correlates with the emm type
These GAS isolates belonged to the emm1 (n = 15), emm28 (n = 13) and emm89 (n = 12) that are the most prevalent emm types circulating in France, and in other European countries and Northern America (Table S1)

Summary

Introduction

Group A Streptococcus (GAS, Streptococcus pyogenes) is among the most ubiquitous and versatile human bacterial pathogen with major healthcare and economic impacts [1,2]. This Gram-positive bacterium can cause a broad range of diseases, from self-limiting suppurative infection of the upper respiratory tract (pharyngitis) and skin (impetigo) to deeper and life threatening invasive infections such as toxic shock-like syndrome (STSS), necrotizing fasciitis (NF), with an estimated 500,000 deaths yearly [1,2]. Since the late 1980’s a marked increase of GAS invasive infections has been reported world-wide [1]. While correlation between emm types and tissue tropism has been reported no link with disease severity has been highlighted except for emm and emm strains, that are associated with NF and STSS [6,7]

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