Murine neutrophils treated with alphaB-crystallin reduce IL-12p40 production by dendritic cells.

Neutrophils are essential in the fight against invading pathogens. They utilize antimicrobial effector mechanisms, such as phagocytosis, release of proteases and other antimicrobial products, robust oxidative bursts and neutrophil extracellular traps to combat infections. Neutrophils also modulate immune responses through the production of eicosanoids, cytokines and chemokines, as well as via direct communication with other immune cells. This system of high-intensity offense against pathogens is exquisitely balanced through regulation to limit damage to host tissue. Unfortunately, the control of neutrophils is not failproof. In cases of sterile injury, autoimmunity and even during an infection, neutrophils can cause tissue destruction and become detrimental to the host. For that reason, there is a need to find means to regulate the aberrant activation of these cells. We found that alphaB-crystallin (αBC), a heat-shock protein known to have anti-inflammatory abilities, affects certain properties of mouse neutrophils that subsequently influence the pro-inflammatory state of antigen-presenting cells (APCs). More specifically, αBC mediated small but significant increases in the levels of IL-10 and matrix metalloproteinase 8, and altered hydrogen peroxide secretion by stimulated neutrophils. Further, the heat-shock protein influenced the communication between neutrophils and dendritic cells by decreasing the production of pro-inflammatory cytokines, specifically IL-12p40, by the APCs. αBC could thus contribute to dampening neutrophil inflammatory responses by impacting the effect of neutrophils on other immune cells.