Different Staphylococcal Strains Elicit Different Levels of Production of t-helper 1-inducing Cytokines

Abstract

Cytokine production has been implicated in the pathogenic mechanisms of infections caused by the staphylococci, since these bacteria may act as strong cytokine inducers. To gain deeper insight into the Th1 immune response activated by these bacteria, we have analyzed the interferon (IFN), interleukin-12 (IL-12) and IL-18-inducing activities of different Staphylococcus aureus (S. aureus), S. epidermidis and S. saprophyticus strains in human monocytes and murine bone marrow macrophages. A large majority of the S. aureus strains elicited the simultaneous production of IL-12 p70 and IFN-alpha in the human monocytes, while the S. epidermidis and S. saprophyticus strains induced only a low level of production, if any, of these cytokines. Furthermore, a majority of the S. aureus strains induced significantly higher IL-12 p70 and IL-18 titers in the murine bone marrow macrophages than did the S. epidermidis and S. saprophyticus strains. As IL-12, IL-18 and IFN-alpha stimulate Th1 differentiation synergistically, we suggest that S. aureus strains bias the immune response toward a Th1 phenotype, whereas S. epidermidis and S. saprophyticus strains provide a weaker stimulus for the production of Th1-inducing cytokines, and accordingly possibly elicit a less extensive Th1-associated adaptive immunity.

Poly(trimethylene carbonate) and poly(D,L-lactic acid) modify human dendritic cell responses to staphylococci but do not affect Th1 and Th2 cell development

“…Moreover, S. aureus was a strong inducer of T cell proliferation and Th1 cell development in contrast to S. epidermidis. Consistent with our results, S. aureus is shown to be a more potent inducer of IFN and IL-12p70 production by human mononuclear cells than S. epidermidis (Buzas et al, 2004). The mechanism underlying the enhanced DC cytokine response to S. aureus is still to be elucidated, but it may be related to the multiple virulence factors expressed by S. aureus, such as staphylococcal enterotoxins (Coutant et al, 1999;Stuyt et al, 2001).…”

Suppression of the Inflammatory Immune Response Prevents the Development of Chronic Biofilm Infection Due to Methicillin-Resistant Staphylococcus aureus

“…Because neutralization of IL-12 p40 resulted in significantly lower infection rates, it is possible that there is a cumulative effect that results from the combination of Th1 and Th17 responses, both of which may be required to exacerbate chronic infection. Th1 and Th17 responses both lead to the release of a myriad of proinflammatory cytokines and to migration and activation of neutrophils (8,25,50). Therefore, by suppressing these inflammatory host responses, conditions that promote biofilm formation in the host are limited and S. aureus infection may be less able to develop into a chronic biofilm infection.…”

“…This skewing in turn influences the propensity of S. aureus infection to progress from an acute infection to a biofilm infection that is chronic. During the early stages of an S. aureus infection, host innate immune cells, such as monocytes, produce a number of proinflammatory cytokines, including IL-1, IL-6, IL-12 p70, IL-18, and TNF-␣ (8,42). This cytokine milieu drives proinflammatory Th1 and Th17 CD4 ϩ T helper cell responses that can result in substantial damage to host tissues.…”

Understanding the significance of Staphylococcus epidermidis bacteremia in babies and children

“…Interestingly, whole blood from term neonates can be as efficient at producing cytokines compared to that of adults in response to in vitro stimulation with S. epidermidis [77•]. Generally, production of cytokines is significantly lower as a response to S. epidermidis compared to S. aureus [78, 79•]. However, in chronic S. epidermidis biofilm-associated infections, a cellular immune response may be initiated as indicated by the production of high levels of IL-1β, IL-12 and gamma interferon (IFN-γ) by human leukocytes in an in vitro biofilm model [80].…”