1. Department of Immunology, University of Washington, H-574 Health Sciences, Box 357650, Seattle, Washington 98195, USA
2. These authors contributed equally to this work

Correspondence to: Alan Aderem Correspondence and requests for materials should be addressed to A.A. (e-mail: Email: aaderem@u.washington.edu).

Abstract

Macrophages orchestrate innate immunity by phagocytosing pathogens and coordinating inflammatory responses¹. Effective defence requires the host to discriminate between different pathogens. The specificity of innate immune recognition in Drosophila is mediated by the Toll family of receptors^{2, 3}; Toll mediates anti-fungal responses, whereas 18-wheeler mediates anti-bacterial defence^{4, 5, 6}. A large number of Toll homologues have been identified in mammals, and Toll-like receptor 4 is critical in responses to Gram-negative bacteria^{7, 8, 9, 10, 11}. Here we show that Toll-like receptor 2 is recruited specifically to macrophage phagosomes containing yeast, and that a point mutation in the receptor abrogates inflammatory responses to yeast and Gram-positive bacteria, but not to Gram-negative bacteria. Thus, during the phagocytosis of pathogens, two classes of innate immune receptors cooperate to mediate host defence: phagocytic receptors, such as the mannose receptor, signal particle internalization, and the Toll-like receptors sample the contents of the vacuole and trigger an inflammatory response appropriate to defence against the specific organism.

1. Department of Immunology, University of Washington, H-574 Health Sciences, Box 357650, Seattle, Washington 98195, USA
2. These authors contributed equally to this work

Correspondence to: Alan Aderem Correspondence and requests for materials should be addressed to A.A. (e-mail: Email: aaderem@u.washington.edu).