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Cited by 274Immune cells in cancerPhagocytosis and Immune RegulationParasites and Host Interactions

Alternative activation is an innate response to injury that requires CD4+ T cells to be sustained during chronic infection

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Loke, P’ng, Gallagher, Iain, Nair, Meera G, Zang, Xingxing, Brombacher, Frank, Mohrs, Markus, Allison, James P, Allen, Judith E·2007·The Journal of Immunology
DOI 10.4049/jimmunol.179.6.3926
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Abstract

Alternatively activated macrophages (AAMPhi) are found in abundance during chronic Th2 inflammatory responses to metazoan parasites. Important roles for these macrophages are being defined, particularly in the context of Th2-mediated pathology and fibrosis. However, a full understanding of the requirements for alternative activation, particularly at the innate level, is lacking. We present evidence that alternative activation by the Th2 cytokines IL-4 and IL-13 is an innate and rapid response to tissue injury that takes place even in the absence of an infectious agent. This early response does not require CD4+ Th2 cells because it occurred in RAG-deficient mice. However, class II-restricted CD4+ T cell help is essential to maintain AAMPhi in response to infection, because AAMPhi were absent in RAG-deficient and MHC class II-deficient, but not B cell-deficient mice after chronic exposure to the nematode parasite, Brugia malayi. The absence of AAMPhi was associated with increased neutrophilia and reduced eosinophilia, suggesting that AAMPhi are involved in the clearance of neutrophils as well as the recruitment of eosinophils. Consistent with this hypothesis, AAMPhi show enhanced phagocytosis of apoptotic neutrophils, but not latex beads. Our data demonstrate that alternative activation by type 2 cytokines is an innate response to injury that can occur in the absence of an adaptive response. However, analogous to classical activation by microbial pathogens, Th2 cells are required for maintenance and full activation during the ongoing response to metazoan parasites.

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  • Genetic deletion of IL-4Rα greatly reduces mRNA expression of the M2a markers Ym1, FIZZ1, and arginase-1 in peritoneal exudate cells after peritoneal incisional wounding in mice.

    “Genetic deletion of IL-4R␣ greatly reduces mRNA expression of the M2a markers Ym1, FIZZ1, and arginase-1 in peritoneal exudate cells (which include Mp, neutrophils, eosinophils, and lymphocytes) after peritoneal incisional wounding in mice [70], indicating that IL-4/-13 are important phenotypic regulators in this model.”

    From Macrophage phenotypes during tissue repair (2013) · cites this paper as [70]

  • After peritoneal incisional wounding, peritoneal exudate cells transiently express elevated Ym1 and FIZZ1 mRNA, although this cell population contains lymphocytes and neutrophils in addition to Mp.

    “Similarly, after peritoneal incisional wounding, peritoneal exudate cells transiently express elevated Ym1 and FIZZ1 mRNA, although this cell population contains lymphocytes and neutrophils in addition to Mp [70], and each of these cell types could express one or both genes [76,77].”

    From Macrophage phenotypes during tissue repair (2013) · cites this paper as [70]

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Authors
Loke, P., Gallagher, I., Nair, M. G., Zang, X., Brombacher, F., Mohrs, M., Allison, J. P., & Allen, J. E.
Affiliations
  • University of California, San Francisco (US)
  • University of Edinburgh (GB)
  • Memorial Sloan Kettering Cancer Center (US)
  • University of Cape Town (ZA)
  • Trudeau Institute (US)
ORCID
Venue
The Journal of Immunology
Publisher
Oxford University Press (OUP)
Published
2007-09
Volume
179
Issue
6
Pages
3926-3936
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
DOI
10.4049/jimmunol.179.6.3926
OpenAlex
W2152215671
Cited by
274
References
73
Citations by year
2026: 2 · 2025: 6 · 2024: 10 · 2023: 1 · 2022: 4 · 2021: 9 · 2020: 5 · 2019: 5 · 2018: 18 · 2017: 15 · 2016: 19 · 2015: 21 · 2014: 22 · 2013: 26 · 2012: 31
FWCI
6.56
Type
journal article
Language
en
Open access
Licence
Locations
  • The Journal of Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • Research Explorer (The University of Manchester) (publishedVersion)
  • Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
Funders
  • Wellcome Trust
  • Medical Research Council
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
  • Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
  • Life Sciences › Immunology and Microbiology › Parasitology › Parasites and Host Interactions
Keywords
alternative activation, M2 macrophages, CD4+ T cells, Th2 cytokines, IL-4, IL-13, tissue damage, innate immunity, chronic infection, Brugia malayi, MHC class II, RAG-deficient mice, eosinophilia, neutrophilia, metazoan parasites
MeSH terms
Animals, Arginase, beta-N-Acetylhexosaminidases, Cell Movement, Chronic Disease, Female, Filariasis, Immunity, Active, Macrophage Activation, Male, Mice, Inbred C57BL, Neutrophils, Proteins, CD4-Positive T-Lymphocytes, Brugia malayi, Mice, Knockout, Nerve Growth Factor, Intercellular Signaling Peptides and Proteins, Lectins, Mice

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