Thymosin α 1 activates dendritic cells for antifungal Th1 resistance through Toll-like receptor signaling

Luigina Romani, Francesco Bistoni, Roberta Gaziano, Silvia Bozza, Claudia Montagnoli, Katia Perruccio, Lucia Pitzurra, Silvia Bellocchio, Andrea Velardi, Guido Rasi, Paolo Di Francesco, Enrico Garaci

Research output: Contribution to journalArticlepeer-review

Abstract

Dendritic cells (DCs) show a remarkable functional plasticity in the recognition of Aspergillus fumigatus and orchestrate the antifungal immune resistance in the lungs. Here, we show that thymosin α 1, a naturally occurring thymic peptide, induces functional maturation and interleukin-12 production by fungus-pulsed DCs through the p38 mitogen-activated protein kinase/ nuclear factor (NF)-κB-dependent pathway. This occurs by signaling through the myeloid differentiation factor 88-dependent pathway, involving distinct Toll-like receptors. In vivo, the synthetic peptide activates T-helper (Th) cell 1-dependent antifungal immunity, accelerates myeloid cell recovery, and protects highly susceptible mice that received hematopoietic transplants from aspergillosis. By revealing the unexpected activity of an old molecule, our finding provides the rationale for its therapeutic utility and qualify the synthetic peptide as a candidate adjuvant promoting the coordinated activation of the innate and adaptive Th immunity to the fungus.

Original languageEnglish
Pages (from-to)4232-4239
Number of pages8
JournalBlood
Volume103
Issue number11
DOIs
Publication statusPublished - Jun 1 2004

ASJC Scopus subject areas

  • Hematology

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