Apoptotic neutrophils augment the inflammatory response to Mycobacterium tuberculosis infection in human macrophages.
Macrophages in the lung are the primary cells being infected by Mycobacterium tuberculosis (Mtb) during the initial manifestation of tuberculosis. Since the adaptive immune response to Mtb is delayed, innate immune cells such as macrophages and neutrophils mount the early immune protection against t...
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| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0101514 |
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| author | Henrik Andersson Blanka Andersson Daniel Eklund Eyler Ngoh Alexander Persson Kristoffer Svensson Maria Lerm Robert Blomgran Olle Stendahl |
| author_facet | Henrik Andersson Blanka Andersson Daniel Eklund Eyler Ngoh Alexander Persson Kristoffer Svensson Maria Lerm Robert Blomgran Olle Stendahl |
| author_sort | Henrik Andersson |
| collection | DOAJ |
| description | Macrophages in the lung are the primary cells being infected by Mycobacterium tuberculosis (Mtb) during the initial manifestation of tuberculosis. Since the adaptive immune response to Mtb is delayed, innate immune cells such as macrophages and neutrophils 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. Since anti-inflammatory activity is not compatible with effective immunity to intracellular pathogens, we therefore investigated how uptake of apoptotic neutrophils modulates the function of Mtb-activated human macrophages. We show that Mtb infection exerts a potent proinflammatory activation of human macrophages with enhanced gene activation and release of proinflammatory cytokines and that this response was augmented by apoptotic neutrophils. 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 contributing to the early control of Mtb infection. |
| format | Article |
| id | doaj-art-d3de8f92fbdd4dc6bf2c789d460f6aaa |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-d3de8f92fbdd4dc6bf2c789d460f6aaa2025-08-20T02:22:49ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0197e10151410.1371/journal.pone.0101514Apoptotic neutrophils augment the inflammatory response to Mycobacterium tuberculosis infection in human macrophages.Henrik AnderssonBlanka AnderssonDaniel EklundEyler NgohAlexander PerssonKristoffer SvenssonMaria LermRobert BlomgranOlle StendahlMacrophages in the lung are the primary cells being infected by Mycobacterium tuberculosis (Mtb) during the initial manifestation of tuberculosis. Since the adaptive immune response to Mtb is delayed, innate immune cells such as macrophages and neutrophils 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. Since anti-inflammatory activity is not compatible with effective immunity to intracellular pathogens, we therefore investigated how uptake of apoptotic neutrophils modulates the function of Mtb-activated human macrophages. We show that Mtb infection exerts a potent proinflammatory activation of human macrophages with enhanced gene activation and release of proinflammatory cytokines and that this response was augmented by apoptotic neutrophils. 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 contributing to the early control of Mtb infection.https://doi.org/10.1371/journal.pone.0101514 |
| spellingShingle | Henrik Andersson Blanka Andersson Daniel Eklund Eyler Ngoh Alexander Persson Kristoffer Svensson Maria Lerm Robert Blomgran Olle Stendahl Apoptotic neutrophils augment the inflammatory response to Mycobacterium tuberculosis infection in human macrophages. PLoS ONE |
| title | Apoptotic neutrophils augment the inflammatory response to Mycobacterium tuberculosis infection in human macrophages. |
| title_full | Apoptotic neutrophils augment the inflammatory response to Mycobacterium tuberculosis infection in human macrophages. |
| title_fullStr | Apoptotic neutrophils augment the inflammatory response to Mycobacterium tuberculosis infection in human macrophages. |
| title_full_unstemmed | Apoptotic neutrophils augment the inflammatory response to Mycobacterium tuberculosis infection in human macrophages. |
| title_short | Apoptotic neutrophils augment the inflammatory response to Mycobacterium tuberculosis infection in human macrophages. |
| title_sort | apoptotic neutrophils augment the inflammatory response to mycobacterium tuberculosis infection in human macrophages |
| url | https://doi.org/10.1371/journal.pone.0101514 |
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