Kinin receptor expression during Staphylococcus aureus infection

Abstract

An inappropriate host response to invading bacteria is a critical parameter that often aggravates the outcome of an infection. Staphylococcus aureus is a major human Gram-positive pathogen that causes a wide array of community-and hospital-acquired diseases ranging from superficial skin infections to severe conditions such as staphylococcal toxic shock. Here we find that S aureus induces inflammatory reactions by modulating the expression and response of the B1 and B2 receptors, respectively. This process is initiated by a chain of events, involving staphylococcal-induced cytokine release from monocytes, bacteriatriggered contact activation, and conversion of bradykinin to its metabolite IntroductionStaphylococcus aureus, an important opportunistic Gram-positive human pathogen, is the most common organism isolated from soft-tissue and wound infections. The bacterium can cause a variety of community-and hospital-acquired diseases ranging from relatively benign skin infections, such as furuncles and subcutaneous abscesses, to more severe conditions, including scaled skin syndrome, necrotizing pneumonia, endocarditis, sepsis, and staphylococcal toxic shock syndrome (for reviews, see Lowy 1 and Yarwood and Schlievert 2 ). In severe conditions, staphylococci may evoke an inappropriate inflammatory host response by modulating so-called host effector systems. For instance, S aureus produces a diverse range of virulence factors contributing to the inflammatory response, among others the enterotoxins and toxic shock syndrome toxin-1 (TSST-1) that form a class of substances also known as pyrogenic toxin superantigens or PTSAgs (for a review, see Balaban and Rasooly 3 ). PTSAgs can induce a profound inflammatory reaction by interacting with MHC class II molecules and T-cell antigen receptors disengaged from the normal antigen-specific signal transduction of T cells. 4,5 The resulting inflammatory response is by far greater than antigen-specific activation and leads to pathologic levels of proinflammatory cytokines. 6 The human contact system, also known as the kallikrein-kinin cascade or intrinsic pathway of coagulation, is another example of a system that can be targeted and affected during infection. 7 The contact system consists of 4 factors, 3 serine proteinases (coagulation factors XI and XII, and plasma kallikrein), and 1 nonenzymatic cofactor (high-molecular-weight kininogen). Normally, these factors circulate as zymogens in the bloodstream. Contact activation can occur for instance on newly exposed cellular surfaces and is regulated by limited proteolysis. The initial step is activation of coagulation factor XII, which converts plasma kallikrein into the active form. Active kallikrein in turn amplifies the activation of factor XII, eventually resulting in clot formation, and the release of bradykinin (BK) from the precursor molecule, high-molecularweight kininogen. Previous studies have shown an interaction between S aureus and the contact system leading to its activation at the bacterial surface. 8 As a result, B...

Streptococcus pyogenes Triggers Activation of the Human Contact System by Streptokinase

“…This mechanism could explain the in vivo contact activation and bradykinin liberation seen during streptococcal invasive infections (2,11,33,38). Local and controlled activation of the contact system has been discussed to promote bacterial invasive spread via bradykinin-induced vascular leakage, since inflowing nutrient-rich plasma to the infected tissue site might serve as a route for the disseminating pathogen (6,22,36,39). On the other hand, the systemic activation of the contact cascade is supposed to contribute to the pathophysiology of severe invasive infections.…”

“…Many invasive pathogens exploit plasmin as a virulence factor to degrade fibrin clots, overcome tissue barriers, and evade peptide-derived host immune defenses (34,35). Under normal conditions, soluble plasmin is immediately inhibited by ␣2-antiplasmin (6,22,32,36); however, the SK-plasmin complex is protected from this inhibitor and promotes uncontrolled plasmin activity. We found that the degradation of HK by SK generates high levels of bradykinin and can be induced independently of PK.…”

Upregulaton of Bradykinin Receptor Mediated by Nucleoside Diphosphate Kinase and Flagellin from Pseudomonas aeruginosa

“…B1R은 주 로 급성 통증 유발과 관련이 있으며, B1R-리간드 반응에 의해 CXCL5와 같은 케모카인의 발현을 유도하여 neutrophil을 감염 부위로 침윤시킬 수 있다 (Duchene et al, 2007). Bradykinin 2 Receptor (B2R)는 여러 조직에 널리 분포하고 있으며, 활성화되 면 혈관 팽창을 통해 염증반응을 돕는 것으로 알려져 있다 (Hall, 1997 (Bengtson et al, 2006;Kaman et al, 2009;Ha, 2011a, 2011b 져 있다 (Kolli et al, 2008). 본 연구에서는, 녹농균에 의한 BR 발현 증가에 Ndk가 관여하며, 이러한 효과는 주요 PAMP로 알 려진 flagella가 함께 필요함을 규명하였다.…”

“…Previously, we reported that expression of the bradykinin receptor (BR) is induced in response to et al, 2006;Kaman et al, 2009; Ha, 2011a, 2011b …”

Degradation of human kininogens with the release of kinin peptides by extracellular proteinases of Candida spp.

“…Additionally, a microbial proteinase-independent activation of the host plasma kininforming system was recently suggested to proceed after adsorption of its proteinaceous components on Candida spp. cell walls Karkowska-Kuleta et al, 2010), a mechanism also extensively characterized for numerous bacterial pathogens (Ben Nasr et al, 1995Mattsson et al, 2001;Bengtson et al, 2006). However, a direct kininogenase activity of candidial proteinases has not yet been described.…”