Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Tratamiento Farmacológico de COVID-19 , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , SARS-CoV-2 , WashingtónRESUMEN
Modulins represent microbial products that stimulate cytokine production in host cells. The modulins responsible for gram-positive sepsis remain poorly understood. Staphylococci release a factor (or factors) that activates nuclear factor-kappa B and stimulates cytokine production in cells of macrophage lineage. This factor, termed phenol-soluble modulin (PSM), has been recently isolated from culture supernatant of Staphylococcus epidermidis. We examined the effects of PSM on proinflammatory properties of human neutrophils and monocytes in vitro. PSM activated the respiratory (oxidative) burst in neutrophils and primed neutrophils for enhanced respiratory burst activity in response to formyl-methionyl-leucyl-phenylalanine. PSM also stimulated neutrophil degranulation as reflected by increased surface expression of CD11b and CD18, which was accompanied by rapid shedding of L-selectin. Spontaneous apoptosis of both neutrophils and monocytes was inhibited by PSM. Furthermore, PSM also functioned as a chemoattractant factor for both neutrophils and monocytes. Thus, the proinflammatory properties of PSM resemble those of both lipopolysaccharide and bacterial chemotactic peptides. These findings suggest that PSM may play a role in the pathogenesis and systemic manifestations of sepsis caused by staphylococci.
Asunto(s)
Toxinas Bacterianas/inmunología , Monocitos/inmunología , Neutrófilos/inmunología , Apoptosis/inmunología , Antígenos CD18/biosíntesis , Quimiotaxis de Leucocito/inmunología , Humanos , Selectina L/biosíntesis , Antígeno de Macrófago-1/biosíntesis , Monocitos/metabolismo , Activación Neutrófila/inmunología , Neutrófilos/metabolismo , Estallido Respiratorio/inmunología , Infecciones Estafilocócicas/inmunología , Staphylococcus epidermidis/química , Staphylococcus epidermidis/inmunología , Staphylococcus epidermidis/metabolismoRESUMEN
Toll-like receptor (TLR) 2 and TLR4 play important roles in the early, innate immune response to microbial challenge. TLR2 is preferentially involved in the inflammatory response to lipoteichoic acid, lipopeptides, and glycans from a variety of microbes, whereas TLR4 is essential for a complete response to LPSs. We report here that TLR2 transduces the response to phenol-soluble modulin, a factor secreted by Staphylococcus epidermidis. The TLR2-mediated response to this modulin was enhanced by TLR6 but inhibited by TLR1, indicating a functional interaction between these receptors. We also demonstrate that a response to phenol-soluble modulin mediated by TLR2 and TLR6 was more refractory to inhibition by TLR1 than one mediated by TLR2 alone.