Role of JAK-STAT signaling in maturation of phagosomes containing Staphylococcus aureus

Abstract

Phagocytosis is a required mechanism for the defense against pathogens. Staphylococcus aureus, an important bacterial pathogen, can promptly escape from phagosomes and proliferate within the cytoplasm of host. However, the mechanism of phagocytosis against S. aureus has not been intensively investigated. In this study, the S. aureus was engulfed by macrophages (RAW264.7 cells) but not digested by the cells, suggesting that the phagosomes did not maturate in macrophages. Further investigation revealed that peptidoglycan (PG) induced the phagosome maturation of macrophages, resulting in the eradication of S. aureus. Genome-wide analysis and quantitative real-time PCR indicated that the JAK-STAT pathway was activated by PG during the phagosome maturation of macrophages against S. aureus. This finding presented that the PG-activated JAK-STAT pathway was required for phagosome maturation. Therefore, our study contributed evidence that revealed a novel aspect of PG-triggered JAK-STAT pathway in the phagosome maturation of macrophages.

Macrophages reprogram after ischemic stroke and promote efferocytosis and inflammation resolution in the mouse brain

“…First, we used IPA to examine the activation/inhibition status of several canonical signaling pathways known to be involved in phagocytic functions (Figure A). A large number of signaling pathways which are known to promote phagocytic activities were predicted to be significantly activated ( z ‐score >2, P < .01) in macrophages from the poststroke brain, such as the TREM1 signaling, ERK5 signaling, JAK/STAT signaling, and PI3K/AKT signaling pathways (Figure A). Consistently, the PTEN signaling pathway, which is an endogenous inhibiting signal of phagocytosis, was predicted to be strongly inhibited ( z ‐score <−2, P < .01; Figure A) in brain macrophages after cerebral ischemia, further supporting the overall enhanced phagocytic capacity of brain macrophages.…”

Novel Resolvin D2 Receptor Axis in Infectious Inflammation

“…In addition, RAW264.7 murine macrophage phagocytosis of Staphylococcus aureus leads to up-regulation of genes involved in JAK-STAT pathway, including STAT3 and STAT5. Phosphorylation of STAT3 and STAT5 proteins is required for phagosome acidification and maturation (53). Thus, it is likely that STAT3 phosphorylation is also required for phagosome maturation during human macrophages phagocytosis.…”

Papel de Fast ("Fas-activated serine threonine phosphoprotein") en la fagocitosis de las bacterias por parte de los macrófagos

“…Las diferencias estructurales entre gram positivos y gram negativos antes mencionadas, pueden explicar el porqué en ausencia de opsoninas, Staphylococcus aureus es más fácilmente fagocitado por los macrófagos peritoneales de ratones comparado con Escherichia coli. El peptidoglicano que es un componente muy abundante en las paredes celulares de las bacterias gram positivas y juega un papel muy importante en la fagocitosis de estas bacterias a través de TLR2 (115). Por su parte, el LPS es un componente principal de las paredes celulares de las bacterias gram negativas e inducen a los macrófagos para fagocitar las bacterias gram negativas a través de los TLR4 (115).…”

“…El peptidoglicano que es un componente muy abundante en las paredes celulares de las bacterias gram positivas y juega un papel muy importante en la fagocitosis de estas bacterias a través de TLR2 (115). Por su parte, el LPS es un componente principal de las paredes celulares de las bacterias gram negativas e inducen a los macrófagos para fagocitar las bacterias gram negativas a través de los TLR4 (115).…”

“…La proteína A que es un componente de la pared celular de S. aureus, puede contribuir a la formación de biopelículas para prevenir la fagocitosis. El ácido lipoteicoico y el factor de aglutinación A que es una proteína de la superficie de unión a fibrinógeno de S. aureus, pueden interferir e inhibir la fagocitosis de los leucocitos contra S. aureus (115). Pensamos que ambos factores explican las diferencias de porcentajes de fagocitosis entre bacterias gram negativas y gram positivas como se observa en la figura 24.…”