Apoptotic neutrophils augment the inflammatory response to Mycobacterium tuberculosis infection in human macrophages
2014 (English)In: PLoS ONE, ISSN 1932-6203, Vol. 9, no 7, e101514- p.Article in journal (Refereed) Published
Macrophages in the lung are the primary cells being infected by Mycobacterium tuberculosis (Mtb) during tuberculosis. Innate immune cells such as macrophages and neutrophils are first recruited to the site of infection, and mount the early immune protection against this intracellular pathogen. Neutrophils are short-lived cells and removal of apoptotic cells by resident macrophages is a key event in the resolution of inflammation and tissue repair. Such anti-inflammatory activity is not compatible with effective immunity to intracellular pathogens. We therefore investigated how uptake of apoptotic neutrophils by Mtb-activated human monocyte-derived macrophages modulates their function. We show that Mtb infection exerts a potent pro-inflammatory activation of human macrophages with enhanced gene activation and release of several cytokines (TNF, IL-1ß, IL-6, IL-18 and IL-10). This response was augmented by apoptotic neutrophils. Macrophages containing both Mtb and apoptotic cells showed a stronger cytokine expression than non-infected cells. The enhanced macrophage response is linked to apoptotic neutrophil-driven activation of the NLRP3 inflammasome and subsequent IL-1β signalling. We also demonstrate that apoptotic neutrophils not only modulate the inflammatory response, but also enhance the capacity of infected macrophages to control intracellular growth of virulent Mtb. Taken together, these results suggest a novel role for apoptotic neutrophils in the modulation of the macrophage-dependent inflammatory response, which can contribute to the early control of Mtb infection.
Place, publisher, year, edition, pages
PLoS , 2014. Vol. 9, no 7, e101514- p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-100888DOI: 10.1371/journal.pone.0101514ISI: 000338637300054OAI: oai:DiVA.org:liu-100888DiVA: diva2:664164