HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hernandez, Y. Articles by Huffnagle, G. B. Search for Related Content PubMed PubMed Citation Articles by Hernandez, Y. Articles by Huffnagle, G. B.

Distinct Roles for IL-4 and IL-10 in Regulating T2 Immunity during Allergic Bronchopulmonary Mycosis¹

Yadira Hernandez^*,, Shikha Arora^*, John R. Erb-Downward^*,, Roderick A. McDonald^*, Galen B. Toews^* and Gary B. Huffnagle^2,*,

^* Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine and Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109

Pulmonary Cryptococcus neoformans infection of C57BL/6 mice is an established model of an allergic bronchopulmonary mycosis that has also been used to test a number of immunomodulatory agents. Our objective was to determine the role of IL-4 and IL-10 in the development/manifestation of the T2 response to C. neoformans in the lungs and lung-associated lymph nodes. In contrast to wild-type (WT) mice, which develop a chronic infection, pulmonary clearance was significantly greater in IL-4 knockout (KO) and IL-10 KO mice but was not due to an up-regulation of a non-T cell effector mechanism. Pulmonary eosinophilia was absent in both IL-4 KO and IL-10 KO mice compared with WT mice. The production of IL-4, IL-5, and IL-13 by lung leukocytes from IL-4 KO and IL-10 KO mice was lower but IFN- levels remained the same. TNF- and IL-12 production by lung leukocytes was up-regulated in IL-10 KO but not IL-4 KO mice. Overall, IL-4 KO mice did not develop the systemic (lung-associated lymph nodes and serum) or local (lungs) T2 responses characteristic of the allergic bronchopulmonary C. neoformans infection. In contrast, the systemic T2 elements of the response remained unaltered in IL-10 KO mice whereas the T2 response in the lungs failed to develop indicating that the action of IL-10 in T cell regulation was distinct from that of IL-4. Thus, although IL-10 has been reported to down-regulate pulmonary T2 responses to isolated fungal Ags, IL-10 can augment pulmonary T2 responses if they occur in the context of fungal infection.

This article has been cited by other articles:

				G.-h. Chen, D. A. McNamara, Y. Hernandez, G. B. Huffnagle, G. B. Toews, and M. A. Olszewski Inheritance of Immune Polarization Patterns Is Linked to Resistance versus Susceptibility to Cryptococcus neoformans in a Mouse Model Infect. Immun., June 1, 2008; 76(6): 2379 - 2391. [Abstract] [Full Text] [PDF]

				U. Muller, W. Stenzel, G. Kohler, C. Werner, T. Polte, G. Hansen, N. Schutze, R. K. Straubinger, M. Blessing, A. N. J. McKenzie, et al. IL-13 Induces Disease-Promoting Type 2 Cytokines, Alternatively Activated Macrophages and Allergic Inflammation during Pulmonary Infection of Mice with Cryptococcus neoformans J. Immunol., October 15, 2007; 179(8): 5367 - 5377. [Abstract] [Full Text] [PDF]

				J. E. Milam, A. C. Herring-Palmer, R. Pandrangi, R. A. McDonald, G. B. Huffnagle, and G. B. Toews Modulation of the Pulmonary Type 2 T-Cell Response to Cryptococcus neoformans by Intratracheal Delivery of a Tumor Necrosis Factor Alpha-Expressing Adenoviral Vector Infect. Immun., October 1, 2007; 75(10): 4951 - 4958. [Abstract] [Full Text] [PDF]

				G.-H. Chen, M. A. Olszewski, R. A. McDonald, J. C. Wells, R. Paine III, G. B. Huffnagle, and G. B. Toews Role of Granulocyte Macrophage Colony-Stimulating Factor in Host Defense Against Pulmonary Cryptococcus neoformans Infection during Murine Allergic Bronchopulmonary Mycosis Am. J. Pathol., March 1, 2007; 170(3): 1028 - 1040. [Abstract] [Full Text] [PDF]

				S. Arora, R. A. McDonald, G. B. Toews, and G. B. Huffnagle Effect of a CD4-Depleting Antibody on the Development of Cryptococcus neoformans-Induced Allergic Bronchopulmonary Mycosis in Mice Infect. Immun., July 1, 2006; 74(7): 4339 - 4348. [Abstract] [Full Text] [PDF]

				N. E. Mangan, N. van Rooijen, A. N. J. McKenzie, and P. G. Fallon Helminth-Modified Pulmonary Immune Response Protects Mice from Allergen-Induced Airway Hyperresponsiveness J. Immunol., January 1, 2006; 176(1): 138 - 147. [Abstract] [Full Text] [PDF]

				S. Arora, Y. Hernandez, J. R. Erb-Downward, R. A. McDonald, G. B. Toews, and G. B. Huffnagle Role of IFN-{gamma} in Regulating T2 Immunity and the Development of Alternatively Activated Macrophages during Allergic Bronchopulmonary Mycosis J. Immunol., May 15, 2005; 174(10): 6346 - 6356. [Abstract] [Full Text] [PDF]