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

P'Ng Loke, Iain Gallagher, Meera G. Nair, Xingxing Zang, Frank Brombacher, Markus Mohrs, James P. Allison, Judith E. Allen

Research output: Contribution to journalArticle

195 Citations (Scopus)

Abstract

Alternatively activated macrophages (AAMΦ) 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 AAMΦ in response to infection, because AAMΦ 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 AAMΦ was associated with increased neutrophilia and reduced eosinophilia, suggesting that AAMΦ are involved in the clearance of neutrophils as well as the recruitment of eosinophils. Consistent with this hypothesis, AAMΦ 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.

Original languageEnglish (US)
Pages (from-to)3926-3936
Number of pages11
JournalJournal of Immunology
Volume179
Issue number6
StatePublished - Sep 15 2007
Externally publishedYes

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Macrophages
T-Lymphocytes
Wounds and Injuries
Infection
Th2 Cells
Parasites
Neutrophils
Brugia malayi
Cytokines
Interleukin-13
Eosinophilia
Microspheres
Phagocytosis
Eosinophils
Interleukin-4
Fibrosis
B-Lymphocytes
Maintenance
Pathology

ASJC Scopus subject areas

  • Immunology

Cite this

Loke, PN., Gallagher, I., Nair, M. G., Zang, X., Brombacher, F., Mohrs, M., ... Allen, J. E. (2007). Alternative activation is an innate response to injury that requires CD4+ T cells to be sustained during chronic infection. Journal of Immunology, 179(6), 3926-3936.

Alternative activation is an innate response to injury that requires CD4+ T cells to be sustained during chronic infection. / Loke, P'Ng; Gallagher, Iain; Nair, Meera G.; Zang, Xingxing; Brombacher, Frank; Mohrs, Markus; Allison, James P.; Allen, Judith E.

In: Journal of Immunology, Vol. 179, No. 6, 15.09.2007, p. 3926-3936.

Research output: Contribution to journalArticle

Loke, PN, Gallagher, I, Nair, MG, Zang, X, Brombacher, F, Mohrs, M, Allison, JP & Allen, JE 2007, 'Alternative activation is an innate response to injury that requires CD4+ T cells to be sustained during chronic infection', Journal of Immunology, vol. 179, no. 6, pp. 3926-3936.
Loke, P'Ng ; Gallagher, Iain ; Nair, Meera G. ; Zang, Xingxing ; Brombacher, Frank ; Mohrs, Markus ; Allison, James P. ; Allen, Judith E. / Alternative activation is an innate response to injury that requires CD4+ T cells to be sustained during chronic infection. In: Journal of Immunology. 2007 ; Vol. 179, No. 6. pp. 3926-3936.
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