Mycobacterium tuberculosis-induced apoptotic neutrophils trigger a pro-inflammatory response in macrophages through release of heat shock protein 72, acting in synergy with the bacteria

Persson, Alexander,1978-Linköpings universitet,Medicinsk mikrobiologi,Hälsouniversitetet,Division of Medical Microbiology, Department of Molecular and Clinical Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden (author)

Mycobacterium tuberculosis (Mtb) survive inside macrophages by manipulating microbicidal functions such as phago-lysosome fusion, production of reactive oxygen species and nitric oxide, and by rendering macrophages non-responsive to IFN-γ. Mtb-infected lung tissue does however not only contain macrophages, but also significant numbers of infiltrating polymorphonuclear neutrophils (PMN). These are able to phagocytose and kill ingested Mtb, but are short-lived cells that constantly need to be removed from tissues to avoid tissue damage. Phagocytosis of aged or UV-induced apoptotic PMN by macrophages induce an anti-inflammatory response in macrophages. However, in the present study, we show that engulfment of Mtb-induced apoptotic PMN by macrophages initiates secretion of TNF-α from the macrophages, reflecting a pro-inflammatory response. Moreover, Mtb-induced apoptotic PMN up-regulate heat shock proteins 60 and 72 (Hsp60, Hsp72) intracellularly and also release Hsp72 extracellularly. We found that both recombinant Hsp72 and released Hsp72 enhanced the pro-inflammatory response to both Mtb-induced apoptotic PMN and Mtb. This stimulatory effect of the supernatant was abrogated by depleting the Hsp72 with immunoprecipitation. These findings indicate that released Hsp72 from Mtb-infected PMN can trigger macrophage activation during the early stage of Mtb infections, thereby creating a link between innate and adaptive immunity.

Blomgran-Julinder, RobertLinköpings universitet,Medicinsk mikrobiologi,Hälsouniversitetet,Division of Medical Microbiology, Department of Molecular and Clinical Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden(Swepub:liu)robbl96 (author)
Rahman, SaymaLinköpings universitet,Medicinsk mikrobiologi,Hälsouniversitetet,Division of Medical Microbiology, Department of Molecular and Clinical Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden(Swepub:liu)sayra72 (author)
Zheng, LiminDepartment of Biochemistry, College of Life Sciences, Sun Yansen (Zhongshan) University, Guangzhou, People's Republic of China (author)
Stendahl, OlleLinköpings universitet,Medicinsk mikrobiologi,Hälsouniversitetet,Division of Medical Microbiology, Department of Molecular and Clinical Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden(Swepub:liu)ollst48 (author)
Linköpings universitetMedicinsk mikrobiologi (creator_code:org_t)

By the author/editor: Persson, Alexand ...; Blomgran-Julinde ...; Rahman, Sayma; Zheng, Limin; Stendahl, Olle

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Microbiology in ...

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