IFN-alpha/beta signaling is required for polarization of cytokine responses toward a protective type 1 pattern during experimental cryptococcosis

Research output: Contribution to journalArticle

Abstract

The antiviral activities of type I IFNs have long been established. However, comparatively little is known of their role in defenses against nonviral pathogens. We examined here the effects of type I IFNs on host resistance against the model pathogenic yeast Cryptococcus neoformans. After intratracheal or i.v. challenge with this fungus, most mice lacking either the IFN-alpha/beta receptor (IFN-alpha/beta R) or IFN-beta died from unrestrained pneumonia and encephalitis, while all wild-type controls survived. The pulmonary immune response of IFN-beta/BR-/- mice was characterized by increased expression of IL-4, IL-13, and IL-10, decreased expression of TNF-alpha, IFN-gamma, inducible NO synthetase, and CXCL10, and similar levels of IL-12 mRNA, compared with wild-type controls. Histopathological analysis showed eosinophilic infiltrates in the lungs of IFN-alpha/beta(-/-) mice, although this change was less extensive than that observed in similarly infected IFN-gamma R-deficient animals. Type I IFN responses could not be detected in the lung after intratracheal challenge. However, small, but statistically significant, elevations in IFN-beta levels were measured in the supernatants of bone marrow-derived macrophages or dendritic cells infected with C neoformans. Our data demonstrate that type I IFN signaling is required for polarization of cytokine responses toward a protective type I pattern during cryptococcal infection.

Details

Authors
  • Carmelo Biondo
  • Angelina Midiri
  • Maria Gambuzza
  • Elisabetta Gerace
  • Maria Falduto
  • Roberta Galbo
  • Antonella Bellantoni
  • Concetta Beninati
  • Giuseppe Teti
  • Tomas Leanderson
  • Giuseppe Mancuso
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Immunology in the medical area
Original languageEnglish
Pages (from-to)566-573
JournalJournal of Immunology
Volume181
Issue number1
Publication statusPublished - 2008
Publication categoryResearch
Peer-reviewedYes