Patogénesis de asma

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Nat Immunol. Author manuscript; available in PMC 2012 January 6.

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Published in final edited form as:
Nat Immunol. 2009 July ; 10(7): 713–720. doi:10.1038/ni.1738.

Basophils Function as Antigen Presenting Cells for an AllergenInduced TH2 Response
Caroline L. Sokol1, Ngoc-Quynh Chu1, Shuang Yu1, Simone A. Nish1, Terri M.Laufer2, and
Ruslan Medzhitov1
1Howard Hughes Medical Institute and Department of Immunobiology, Yale University School of
Medicine, New Haven, CT 06510, USA
2Immunology

Graduate Group, University of Pennsylvania, Philadelphia, PA 19104, USA

Abstract
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TH2 mediated immune responses are induced upon infection with multicellular parasites and can
be triggered by avariety of allergens. Mechanisms of induction and the antigen-presenting cells
involved in activation of TH2 responses remain poorly defined and the innate immune sensing
pathways activated by parasites and allergens are largely unknown. Basophils are required for the
in vivo induction of TH2 responses by protease allergens. Here we show that basophils also
function as antigen presenting cells.We show that, while dendritic cells were dispensable, antigen
presentation by basophils was necessary and sufficient for allergen-induced activation of TH2
responses in vitro and in vivo. Thus, basophils function as antigen presenting cells for TH2
differentiation in response to protease allergens.

Introduction

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Different CD4+ T helper cell effector lineagescontrol host defenses against distinct classes
of pathogens. TH1 cells provide protective immunity against intracellular bacterial, viral and
protozoan pathogens, TH-17 cells regulate host defense against extracellular bacterial and
fungal pathogens, and TH2 cells orchestrate immunity against multicellular parasites,
including helminths, which are mostly extracellular pathogens1. Inappropriateactivation of
the three arms of adaptive immunity can lead to different types of immunopathologies,
including autoimmunity in the case of TH1 and TH-17 responses, and allergies in the case of
TH2 responses1.
Although the basic aspects of activation of TH1 and TH-17 immune responses are well
characterized, the mechanisms of induction of TH2 immune responses remain obscure. To a
large extentthis reflects our lack of understanding of the mechanisms of innate immune
recognition of ‘type-2 pathogens’. In the case of TH1 and TH-17 immunity, several classes
of pattern recognition receptors, including Toll-like receptors (TLRs) and Dectin-1, detect
bacterial, viral and fungal pathogens through the recognition of conserved molecular
structures characteristic of each pathogen class2-5.These pattern-recognition receptors are
expressed on, among other cell types, dendritic cells (DCs) where they control their
activation, migration to the lymph nodes, and presentation of pathogen-derived antigens to
naive T cells6. In addition to presenting antigens derived from phagocytosed or endocytosed
pathogens, DCs produce other necessary signals for naive CD4+ T cell activation anddifferentiation into the appropriate TH1 or TH-17 effector lineage4,5,7. Importantly, DCs that
Correspondence should be addressed to R.M. (ruslan.medzhitov@yale.edu).
Competing Interests Statement. The authors declare they have no competing financial interests.

Sokol et al.

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present antigens to naive T cells, also provide co-stimulatory molecules and producecytokines (such as interleukin 12 (IL-12), IL-23 and IL-6) that control TH1 and TH-17
differentiation8,9.

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This scenario, however, may not apply to the initiation of TH2 responses. First, unlike
bacterial, fungal and viral pathogens, parasitic worms are far too large to be phagocytosed
by DCs or any other phagocytes. Therefore, in contrast to the situation with...