Severe group A streptococcal toxic shock syndrome presenting as primary peritonitis: a case report and brief review of the literature

Rahman²,

Zhang³

et al. 2012

J Innate Immun

Streptococcal toxic shock syndrome is frequently caused by Streptococcus pyogenes of the M1 serotype. The aim of this study was to determine the role of Ras-homologous (Rho)-kinase signaling in M1 protein-provoked lung damage. Male C57BL/6 mice received the Rho-kinase-specific inhibitor Y-27632 before administration of M1 protein. Edema, neutrophil accumulation and CXC chemokines were quantified in the lung 4 h after M1 protein challenge. Flow cytometry was used to determine Mac-1 expression. Quantitative RT-PCR was used to determine gene expression of CXC chemokine mRNA in alveolar macrophages. M1 protein increased neutrophil accumulation, edema and CXC chemokine formation in the lung as well as enhanced Mac-1 expression on neutrophils. Inhibition of Rho-kinase signaling significantly reduced M1 protein-provoked neutrophil accumulation and edema formation in the lung. M1 protein-triggered pulmonary production of CXC chemokine and gene expression of CXC chemokines in alveolar macrophages was decreased by Y-27632. Moreover, Rho-kinase inhibition attenuated M1 protein-induced Mac-1 expression on neutrophils. We conclude that Rho-kinase-dependent neutrophil infiltration controls pulmonary tissue damage in response to streptococcal M1 protein and that Rho-kinase signaling regulates M1 protein-induced lung recruitment of neutrophils via the formation of CXC chemokines and Mac-1 expression.

Section: Introductionmentioning

confidence: 99%

Streptococcal M1 Protein-Provoked CXC Chemokine Formation, Neutrophil Recruitment and Lung Damage Are Regulated by Rho-Kinase Signaling

Rahman²,

Zhang³

et al. 2012

J Innate Immun

“…GAS virulence factors aid in evading phagocytosis and facilitate in adherence to host cells, leading to colonization and invasion of the host [26, 31-35]. In addition, GAS has a family of bacterial antigens that are associated with streptococcal toxic shock syndrome (STSS) [36, 37]. This family includes SpeA (Streptococcal pyogenic exotoxin A), SpeC, and others that bind to the MHC class II molecules and T cell receptors, resulting in an excessive release of immunomodulators that activate complement, coagulation, and fibrinolytic cascades, resulting in toxic shock and death.…”

Section: Introductionmentioning

confidence: 99%

Postpartum Group AStreptococcusSepsis and Maternal Immunology

Mason

Aronoff

2011

American J Rep Immunol

Group A Streptococcus (GAS) is an historically important agent of puerperal infections and sepsis. The inception of hand-washing and improved hospital hygiene drastically reduced the incidence of puerperal sepsis, but recently the incidence and severity of postpartum GAS infections has been rising for uncertain reasons. Several epidemiological, host, and microbial factors contribute to the risk for GAS infection and mortality in postpartum women. These include the mode of delivery (vaginal vs. caesarean section), the location where labor and delivery occurred, exposure to GAS carriers, the altered immune status associated with pregnancy, the genetic background of the host, the virulence of the infecting GAS strain, and highly specialized immune responses associated with female reproductive tract tissues and organs. This review will discuss the complicated factors that contribute to the increased susceptibility to GAS after delivery and potential reasons for the recent increase observed in morbidity and mortality.

“…Although the pathophysiological mechanisms behind streptococcal toxic shock syndrome (STSS) remain elusive, convincing data have demonstrated that soluble streptococcal M protein of the M1 serotype is not only a potent activator of innate immunity, including activation of neutrophils (20) and monocytes (35), but also that the M1 serotype is predominantly linked to fatal STSS (18,25). It is well recognized that the lung is the most sensitive and critical organ affected in STSS patients (51)(52)(53). In fact, acute lung injury continues to constitute a significant cause of morbidity and mortality in sepsis despite aggressive surgical interventions as well as antibiotic and immunomodulating therapies.…”

mentioning

confidence: 99%

Simvastatin regulates CXC chemokine formation in streptococcal M1 protein-induced neutrophil infiltration in the lung

Rahman

American Journal of Physiology-Lung Cellular and Molecular Phys

et al. 2011

Streptococcus pyogenes of the M1 serotype can cause streptococcal toxic shock syndrome and acute lung injury. Statins exert beneficial effects in septic patients although the mechanisms remain elusive. This study examined effects of simvastatin on M1 protein-provoked pulmonary inflammation and tissue injury. Male C57BL/6 mice were pretreated with simvastatin or a CXCR2 antagonist before M1 protein challenge. Bronchoalveolar fluid and lung tissue were harvested for determination of neutrophil infiltration, formation of edema, and CXC chemokines. Flow cytometry was used to determine Mac-1 expression on neutrophils. Gene expression of CXC chemokines was determined in alveolar macrophages by using quantitative RT-PCR. M1 protein challenge caused massive infiltration of neutrophils, edema formation, and production of CXC chemokines in the lung as well as upregulation of Mac-1 on circulating neutrophils. Simvastatin reduced M1 protein-induced infiltration of neutrophils and edema in the lung. In addition, M1 protein-induced Mac-1 expression on neutrophils was abolished by simvastatin. Furthermore, simvastatin markedly decreased pulmonary formation of CXC chemokines and gene expression of CXC chemokines in alveolar macrophages. Moreover, the CXCR2 antagonist reduced M1 protein-induced neutrophil expression of Mac-1 and accumulation of neutrophils as well as edema formation in the lung. These novel findings indicate that simvastatin is a powerful inhibitor of neutrophil infiltration in acute lung damage triggered by streptococcal M1 protein. The inhibitory effect of simvastatin on M1 protein-induced neutrophil recruitment appears related to reduced pulmonary generation of CXC chemokines. Thus, simvastatin may be a useful tool to ameliorate acute lung injury in streptococcal infections.