Robust Th1 and Th17 Immunity Supports Pulmonary Clearance but Cannot Prevent Systemic Dissemination of Highly Virulent Cryptococcus neoformans H99

The present study dissected the role of a Th2 bias in pathogenesis of Cryptococcus neoformans H99 infection by comparing inhalational H99 infections in wild-type BALB/c and IL-4/IL-13 double knockout mice. H99-infected wild-type mice showed all major hallmarks of Th2 but not Th1/Th17 immunity in the...

Full description

Saved in:

Bibliographic Details
Published in:	The American journal of pathology Vol. 175; no. 6; pp. 2489 - 2500
Main Authors:	Zhang, Yanmei, Wang, Fuyuan, Tompkins, Kristin C, McNamara, Andrew, Jain, Aditya V, Moore, Bethany B, Toews, Galen B, Huffnagle, Gary B, Olszewski, Michal A
Format:	Journal Article
Language:	English
Published:	Bethesda, MD Elsevier Inc 01-12-2009 ASIP American Society for Investigative Pathology
Subjects:	Animals Biological and medical sciences Chemotaxis, Leukocyte Cryptococcosis - immunology Cryptococcosis - pathology Cryptococcus neoformans Cryptococcus neoformans - immunology Cryptococcus neoformans - pathogenicity Disease Progression Interleukin-13 - deficiency Interleukin-13 - genetics Interleukin-13 - immunology Interleukin-17 - immunology Interleukin-4 - deficiency Interleukin-4 - genetics Interleukin-4 - immunology Investigative techniques, diagnostic techniques (general aspects) Macrophage Activation - immunology Medical sciences Mice Mice, Inbred BALB C Mice, Knockout Pathology Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques Regular Reverse Transcriptase Polymerase Chain Reaction T-Lymphocyte Subsets - immunology Th1 Cells - immunology Th2 Cells - immunology Virulence Cryptococcus neoformans Lung Th1 lymphocyte Systemic Clearance Respiratory system Immunity Fungi Prevention Anatomic pathology Dissemination T-Lymphocyte Fungi Imperfecti Disseminated Th17 lymphocyte
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	The present study dissected the role of a Th2 bias in pathogenesis of Cryptococcus neoformans H99 infection by comparing inhalational H99 infections in wild-type BALB/c and IL-4/IL-13 double knockout mice. H99-infected wild-type mice showed all major hallmarks of Th2 but not Th1/Th17 immunity in the lungs and lung-associated lymph nodes. In contrast, the IL-4/13−/− mice developed robust hallmarks of Th1 and Th17 but not Th2 polarization. The IL-4/IL-13 deletion prevented pulmonary eosinophilia, goblet cell metaplasia in the airways and resulted in elevated serum IgE, and a switch from alternative to classical activation of macrophages. The development of a robust Th1/Th17 response and classical activation of macrophages resulted in significant containment of H99 in the lungs of IL-4/13−/− mice compared with unopposed growth of H99 in the lungs of wild-type mice. However, IL-4/13−/− mice showed only 1-week longer survival compared with wild-type mice. The comparison of brain and spleen cryptococcal loads at weeks 2, 3, and 4 postinfection revealed that the systemic dissemination in IL-4/13−/− mice occurred with an approximate 1-week delay but subsequently progressed with similar rate as in the wild-type mice. Furthermore, wild-type and IL-4/13−/− mice developed equivalently severe meningitis/encephalitis at the time of death. These data indicate that the Th2 immune bias is a crucial mechanism for pulmonary virulence of H99, whereas other mechanisms are largely responsible for its central nervous system tropism and systemic dissemination.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0002-9440 1525-2191
DOI:	10.2353/ajpath.2009.090530