The DOI matches its Crossref record; 40 of the 41 references it cites were found in a registry or an index.
TREM-2 promotes macrophage survival and lung disease after respiratory viral infection
Open accessAbstract
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.
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“The knockdown of Trem2 decreasing survival and altering the metabolism of microglia is consistent with previous studies (35,38–40,56,57).”
From Trem2 promotes anti-inflammatory responses in microglia and is suppressed under pro-inflammatory conditions (2020) · cites this paper as [56]
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Alexopoulou, L., Holt, A. C., Medzhitov, R., & Flavell, R. A. (2001) · Nature · doi:10.1038/35099560 · Cited by 6,129
Bouchon, A., Dietrich, J., & Colonna, M. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.10.4991 · Cited by 1,284 · cited 2×
“2, C and D), consistent with the association of TREM-2 and DAP12 phenotype in other systems (Bouchon et al., 2000; Kaifu et al., 2003; Turnbull et al., 2006).”
BackgroundTREM-1 amplifies inflammation and is a crucial mediator of septic shock
Bouchon, A., Facchetti, F., Weigand, M. A., & Colonna, M. (2001) · Nature · doi:10.1038/35074114 · Cited by 1,092
TREM2 mutations implicated in neurodegeneration impair cell surface transport and phagocytosis
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Self-citationTREMs in the immune system and beyond
Colonna, M. (2003) · Nature Reviews Immunology · doi:10.1038/nri1106 · Cited by 701
Self-citationCutting Edge: TREM-2 Attenuates Macrophage Activation
Turnbull, I. R., Gilfillan, S., Cella, M., Aoshi, T., Miller, M., Piccio, L., Hernandez, M., & Colonna, M. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.177.6.3520 · Cited by 688
Deficient signaling in mice devoid of double‐stranded RNA‐dependent protein kinase.
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Dobrijević, A., Korosec, A., Brunner, J. S., Matejovicova, L., Gemza, A., Lakovits, K., Lam, H. S., Lizaso, A. A., Schabbauer, G., Knapp, S., et al. (2026) · Frontiers in Endocrinology · doi:10.3389/fendo.2026.1738472
Deng, W., Chen, Y., Liu, S., Liu, S., Zhang, K., Wang, D., Yu, Z., Zhao, W., Xu, Y., Wang, X., et al. (2026) · Immunity & Inflammation · doi:10.1007/s44466-026-00041-5 · Cited by 1
Shang, X., Maimaiti, N., Tian, F., 廖春波, Sun, H., Zhou, X., Kong, W., Sun, Q., Wang, L., & Ma, X. F. (2026) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2026.1835965
TREM2 drives monocyte-derived macrophage responses to Cryptococcus neoformansPreprint
Abass, A., Ricafrente, A., Trivedi, A., Vichaidit, A., Arshakyan, A., Acharya, S., & Heung, L. J. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.06.10.731331
Zhu, Z., Zhang, M., Xu, Y., Wen, W., Wang, W., Lee, H., & Li, X. (2026) · Veterinary Microbiology · doi:10.1016/j.vetmic.2026.111154
Metadata
- Authors
- Wu, K., Byers, D. E., Jin, X., Agapov, E., Alexander-Brett, J., Patel, A. C., Cella, M., Gilfilan, S., Colonna, M., Kober, D. L., Brett, T. J., & Holtzman, M. J.
- Affiliations
- Washington University in St. Louis (US)
- Pulmonary and Critical Care Medicine, Department of Medicine 1 , 2 , 3 , 4 , and 5
- Corresponding author
- Holtzman, Michael J.
- ORCID
- Venue
- Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2015-04-20
- Volume
- 212
- Issue
- 5
- Pages
- 681-697
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC4419356
- OpenAlex
- W2111240640
- Cited by
- 207
- References
- 41
- Citations by year
- 2026: 11 · 2025: 17 · 2024: 19 · 2023: 23 · 2022: 36 · 2021: 24 · 2020: 22 · 2019: 8 · 2018: 14 · 2017: 16 · 2016: 11 · 2015: 4
- FWCI
- 7.33
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL119813, P01HL029594, R01HL073159, R01HL121791, P50HL084922, T32HL007317)
- National Institute of Allergy and Infectious Diseases (U19-AI07048, U19AI070489)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Asthma and respiratory diseases
- Keywords
- TREM2, macrophage survival, macrophage apoptosis, Sendai virus, respiratory viral infections, IL-13, DAP12, M2 macrophages, Th2 immune response, airway mucus hypersecretion, innate immune activation
- MeSH terms
- Animals, Cell Survival, Immunity, Innate, Lung Diseases, Membrane Glycoproteins, Respirovirus Infections, Receptors, Immunologic, Virus Replication, Macrophages, Alveolar, Apoptosis, Mice, Knockout, Interleukin-13, Sendai virus, Mice
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