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

Biondo, Carmelo; Midiri, Angelina; Gambuzza, Maria; Gerace, Elisabetta; Falduto, Maria; Galbo, Roberta; Bellantoni, Antonella; Beninati, Concetta; Teti, Giuseppe and Leanderson, Tomas LU , et al. (2008) In Journal of Immunology 181(1). p.566-573
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... (More)
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. (Less)
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Journal of Immunology
volume
181
issue
1
pages
566 - 573
publisher
American Association of Immunologists
external identifiers
  • wos:000257404900063
ISSN
1550-6606
language
English
LU publication?
yes
id
34d6505f-e006-4d9b-8bf9-94028c32d184 (old id 1257012)
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http://www.jimmunol.org/cgi/content/abstract/181/1/566
date added to LUP
2008-10-15 08:55:38
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2016-04-16 00:37:26
@article{34d6505f-e006-4d9b-8bf9-94028c32d184,
  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.},
  author       = {Biondo, Carmelo and Midiri, Angelina and Gambuzza, Maria and Gerace, Elisabetta and Falduto, Maria and Galbo, Roberta and Bellantoni, Antonella and Beninati, Concetta and Teti, Giuseppe and Leanderson, Tomas and Mancuso, Giuseppe},
  issn         = {1550-6606},
  language     = {eng},
  number       = {1},
  pages        = {566--573},
  publisher    = {American Association of Immunologists},
  series       = {Journal of Immunology},
  title        = {IFN-alpha/beta signaling is required for polarization of cytokine responses toward a protective type 1 pattern during experimental cryptococcosis},
  volume       = {181},
  year         = {2008},
}