Unknown

Dataset Information

0

TREM-2 promotes macrophage survival and lung disease after respiratory viral infection.


ABSTRACT: Viral infections and type 2 immune responses are thought to be critical for the development of chronic respiratory disease, but the link between these events needs to be better defined. Here, we study a mouse model in which infection with a mouse parainfluenza virus known as Sendai virus (SeV) leads to long-term activation of innate immune cells that drive IL-13-dependent lung disease. We find that chronic postviral disease (signified by formation of excess airway mucus and accumulation of M2-differentiating lung macrophages) requires macrophage expression of triggering receptor expressed on myeloid cells-2 (TREM-2). Analysis of mechanism shows that viral replication increases lung macrophage levels of intracellular and cell surface TREM-2, and this action prevents macrophage apoptosis that would otherwise occur during the acute illness (5-12 d after inoculation). However, the largest increases in TREM-2 levels are found as the soluble form (sTREM-2) long after clearance of infection (49 d after inoculation). At this time, IL-13 and the adapter protein DAP12 promote TREM-2 cleavage to sTREM-2 that is unexpectedly active in preventing macrophage apoptosis. The results thereby define an unprecedented mechanism for a feed-forward expansion of lung macrophages (with IL-13 production and consequent M2 differentiation) that further explains how acute infection leads to chronic inflammatory disease.

SUBMITTER: Wu K 

PROVIDER: S-EPMC4419356 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

altmetric image

Publications

TREM-2 promotes macrophage survival and lung disease after respiratory viral infection.

Wu Kangyun K   Byers Derek E DE   Jin Xiaohua X   Agapov Eugene E   Alexander-Brett Jennifer J   Patel Anand C AC   Cella Marina M   Gilfilan Susan S   Colonna Marco M   Kober Daniel L DL   Brett Tom J TJ   Holtzman Michael J MJ  

The Journal of experimental medicine 20150420 5


Viral infections and type 2 immune responses are thought to be critical for the development of chronic respiratory disease, but the link between these events needs to be better defined. Here, we study a mouse model in which infection with a mouse parainfluenza virus known as Sendai virus (SeV) leads to long-term activation of innate immune cells that drive IL-13-dependent lung disease. We find that chronic postviral disease (signified by formation of excess airway mucus and accumulation of M2-di  ...[more]

Similar Datasets

| S-BSST116 | biostudies-other
| S-EPMC5816042 | biostudies-literature
| S-EPMC6089355 | biostudies-literature
| S-EPMC2575848 | biostudies-literature
| S-EPMC7165744 | biostudies-literature
| S-EPMC7556752 | biostudies-literature
| S-EPMC6322907 | biostudies-literature
| S-EPMC4189665 | biostudies-literature
| S-EPMC8192557 | biostudies-literature
2016-01-20 | E-GEOD-63990 | biostudies-arrayexpress