Recruitment of neutrophil granulocytes to sites of infectious tissue damage is an early event in innate immune responses. Following chemotactic signals neutrophils establish a first line of defense in a swarm-like manner. Intracellular pathogens such as Leishmania major can, however, evade neutrophil-mediated killing and survive inside neutrophils. To achieve this the parasites evolved potent evasion mechanisms. Since neutrophils are a major source of inflammation regulating lipid mediators, we hypothesized that intracellular infection modifies the release of pro- and anti-inflammatory lipid mediators like leukotriene B4 (LTB4) and lipoxin A4 (LXA4), respectively. In the present study, we demonstrated in vitro that L. major-infected primary human neutrophils release an increased amount of LTB4, whereas LXA4 liberation is reduced during the first hours of infection. To investigate whether lipid mediator modulation is a common feature in intracellular infections, we tested the impact of an infection with Anaplasma phagocytophilum. Similarly to L. major, neutrophil infection with A. phagocytophilum led to an enhanced release of LTB4 and decreased LXA4 production. Together, our findings indicate that intracellular infections modulate the lipid mediator profile of neutrophils. This effect is likely to contribute to the survival of the pathogens in neutrophils and to the outcome of the infections.
Research Areas and Centers
- Academic Focus: Center for Infection and Inflammation Research (ZIEL)