IFN-alpha/beta signaling is required for polarization of cytokine responses toward a protective type 1 pattern during experimental cryptococcosis.
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/betaR) or IFN-beta died from unrestrained pneumonia and encephalitis, while all wild-type controls survived. The pulmonary immune response of IFN-alpha/betaR-/- 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/betaR-/- mice, although this change was less extensive than that observed in similarly infected IFN-gammaR-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.
Biondo
Carmelo
C
Dipartimento di Patologia e Microbiologia Sperimentale, Università degli Studi di Messina, Messina, Italy.
Midiri
Angelina
A
Gambuzza
Maria
M
Gerace
Elisabetta
E
Falduto
Maria
M
Galbo
Roberta
R
Bellantoni
Antonella
A
Beninati
Concetta
C
Teti
Giuseppe
G
Leanderson
Tomas
T
Mancuso
Giuseppe
G
D000818:Animals; D002478:Cells, Cultured; D003453:Cryptococcosis / Q000276:immunology* / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology; D004195:Disease Models, Animal; D016898:Interferon-alpha / Q000276:immunology*; D016899:Interferon-beta / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053633:Receptor, Interferon alpha-beta / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D015996:Survival Rate
D016898:Interferon-alpha; D053633:Receptor, Interferon alpha-beta; D016899:Interferon-beta