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-Glucan Is a Fungal Determinant for Adhesion-Dependent Human Neutrophil Functions¹

Liz M. Lavigne^*,, Jorge E. Albina^* and Jonathan S. Reichner^2,*

^* Department of Surgery, Division of Surgical Research, Rhode Island Hospital and Brown University School of Medicine, Providence, RI 02903; and Graduate Program in Pathobiology, Brown University, Providence, RI 02912

Candida albicans is a common cause of nosocomial infections whose virulence depends on the reversible switch from blastoconidia to hyphal forms. Neutrophils (or polymorphonuclear leukocytes (PMNs)) readily clear blastoconidia by phagocytosis, but filaments are too long to be ingested. Mechanisms regulating immune recognition and response to filamentous fungal pathogens are not well understood, although known risk factors for developing life-threatening infections are neutropenia or defects in the NADPH oxidase system. We show human PMNs generate a respiratory burst response to unopsonized hyphae. Ab specific for -glucan, a major component of yeast cell walls, blocks this response, establishing -glucan as a key molecular pattern recognized by PMNs in response to C. albicans. This study also elucidates recognition and signaling mechanisms used by PMNs in response to -glucan under conditions where phagocytosis cannot occur. Human PMNs adhered to immobilized -glucan and released an efficient plasma membrane respiratory burst. Ab blockade of the integrin complement receptor 3 (CD11b/CD18) significantly inhibited both of these functions. Furthermore, we show a role for p38 MAPK and actin but not protein kinase C in generating the respiratory burst to -glucan. Taken together, results show that -glucan in C. albicans hyphae is accessible to PMNs and sufficient to support an innate immune response.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by grants from the National Institutes of Health Grants GM-066194 (to J.S.R.) and GM-42859 (to J.E.A.), Grant Assistance in Areas of National Need from the U.S. Department of Education (to L.M.L.), and allocations to the Department of Surgery by Rhode Island Hospital.

² Address correspondence and reprint requests to Jonathan S. Reichner, Department of Surgery, Rhode Island Hospital, 593 Eddy Street, Providence, RI 02903. E-mail address: Jonathan_Reichner{at}Brown.edu

³ Abbreviations used in this paper: PAMP, pathogen-associated molecular pattern; CR3, complement receptor 3 (CD11b/CD18, Mac-1, or _M2 integrin); dPBS, Dulbecco’s PBS; O₂^–, superoxide anion; Pam₃CSK₄, Pam₃CysSerLys₄; PKC, protein kinase C ; PMN, polymorphonuclear leukocyte or neutrophil; ROS, reactive oxygen species; sBLP, synthetic bacterial lipopeptide; WGP, whole glucan particle; GR, -glucan receptor.

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