Papeis opostos de FcγRIIb e FcγRIII na inflamação articular e no clearance bacteriano na artrite séptica induzida por Staphylococcus aureus

Abstract

Septic arthritis is an articular disease caused by a microorganism. Several viruses, fungi and bacteria can cause this disease, but Staphylococcus aureus is the most common cause, due to its numerous virulence factors and to its ability to evade the immune system. The classic manifestation of septic arthritis includes severe pain, even at rest, edema, increased temperature on site and reduced mobility of the joint. Microorganisms trigger an inflammatory response in the joint that creates the conditions for the recruitment of cells such neutrophils that are granulocytes specialized in the control of microorganisms. Receptors for the Fc portion of immunoglobulin play an important role triggering pro and anti-inflammatory cascades with the release of many cytokines, in order to control the disease and the inflammation. This study aimed to evaluate the role of FcγRIIb and FcγRIII in the bacterial clearance and the inflammatory response in the experimental model of septic arthritis. To this end, mice deficient for these receptors were infected with S. aureus and compared to wild type animals at times determined by preliminary experiments. FcγRIIb-/- animals had an anticipated leukocyte accumulation peak and a reduction of the bacterial load in the joint cavity, associated with increased neutrophil apoptosis and CXCR2 expression. Furthermore, FcγRIIb-/- animals had a greater amount of IL-1 cytokine in the joint on the first day of infection in relation to wild animals. Similar data were obtained on culture of macrophages stimulated with S. aureus. Such increased joint inflammation in the FcγRIIb-/- animals at the beginning of the response may be due to increased signaling by stimulatory FcγR receptors, since there is an increase in the Syk molecule in FcγRIIb deficient macrophages. On the other hand, the animals FcγRIII-/- showed an increase in leukocyte accumulation and bacterial load at later times of infection associated with increased expression of PD1, an exhaust clonal marker. It is concluded, therefore, that FcγR receptors are very important in S. aureus induced septic arthritis, and the absence of the inhibitory receptor FcγRIIb potentiates the inflammatory response in the first moments of infection, facilitating a better elimination of the bacteria. This response may occur as a function of the FcγRIII stimulatory receptor, since its absence impairs the bacterial joint control, maintaining an intense and persistent inflammation, possibly altering the functions of specific lymphocytes.