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Hyphal Als proteins act as CR3 ligands to promote immune responses against Candida albicans.
Zhou, Tingting; Solis, Norma V; Marshall, Michaela; Yao, Qing; Garleb, Rachel; Yang, Mengli; Pearlman, Eric; Filler, Scott G; Liu, Haoping.
Afiliación
  • Zhou T; Department of Biological Chemistry, University of California, Irvine, CA, USA.
  • Solis NV; Division of Infectious Diseases, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
  • Marshall M; Department of Physiology and Biophysics, University of California, Irvine, CA, USA.
  • Yao Q; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
  • Garleb R; Gilead Sciences Inc., Foster City, CA, USA.
  • Yang M; Department of Biological Chemistry, University of California, Irvine, CA, USA.
  • Pearlman E; Department of Biological Chemistry, University of California, Irvine, CA, USA.
  • Filler SG; Zymo Research Corporation, Irvine, CA, USA.
  • Liu H; Department of Physiology and Biophysics, University of California, Irvine, CA, USA.
Nat Commun ; 15(1): 3926, 2024 May 09.
Article en En | MEDLINE | ID: mdl-38724513
ABSTRACT
Patients with decreased levels of CD18 (ß2 integrins) suffer from life-threatening bacterial and fungal infections. CD11b, the α subunit of integrin CR3 (CD11b/CD18, αMß2), is essential for mice to fight against systemic Candida albicans infections. Live elongating C. albicans activates CR3 in immune cells. However, the hyphal ligands that activate CR3 are not well defined. Here, we discovered that the C. albicans Als family proteins are recognized by the I domain of CD11b in macrophages. This recognition synergizes with the ß-glucan-bound lectin-like domain to activate CR3, thereby promoting Syk signaling and inflammasome activation. Dectin-2 activation serves as the "outside-in signaling" for CR3 activation at the entry site of incompletely sealed phagosomes, where a thick cuff of F-actin forms to strengthen the local interaction. In vitro, CD18 partially contributes to IL-1ß release from dendritic cells induced by purified hyphal Als3. In vivo, Als3 is vital for C. albicans clearance in mouse kidneys. These findings uncover a novel family of ligands for the CR3 I domain that promotes fungal clearance.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Candidiasis / Proteínas Fúngicas / Antígenos CD18 / Lectinas Tipo C / Macrófagos Límite: Animals Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Candidiasis / Proteínas Fúngicas / Antígenos CD18 / Lectinas Tipo C / Macrófagos Límite: Animals Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido