NDLI: STAT4-dependent and -independent Th2 responses correlate with protective immunity against lung infection with Pneumocystis murina.

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Developmental expression of IL-12Rß2 on murine naive neonatal T cells counters the upregulation of IL-13R 1 on primary Th1 cells and balances immunity in the newborn.

STAT4-dependent and -independent Th2 responses correlate with protective immunity against lung infection with Pneumocystis murina.

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What is and what should always have been: long-lived plasma cells induced by T cell-independent antigens.

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STAT4-dependent and -independent Th2 responses correlate with protective immunity against lung infection with Pneumocystis murina.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Dunaway, Chad W. Trevor, Jennifer L. Steele, Chad Myers, Riley C. Nelson, Michael P. Morris, Alison
Description	Country affiliation: United States Author Affiliation: Myers RC ( Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.)
Abstract	Although it is clear that the loss of CD4(+) T cells is a predisposing factor for the development of Pneumocystis pneumonia, specific Th mechanisms mediating protection are not well understood. Th1, Th2, and Th17 responses have each been implicated in protective responses during infection. As STAT4 may promote Th1 and Th17 development, yet antagonize Th2 development, we investigated its role in Pneumocystis murina host defense. STAT4 was required for Th1 and, unexpectedly, Th2 responses in the lungs of C57BL/6 (BL/6) and BALB/c mice 14 d postchallenge, but only BALB/c Stat4(-/-) mice demonstrated susceptibility to P. murina lung infection. BL/6 Stat4(-/-), but not BALB/c Stat4(-/-), mice maintained an enhanced alternatively activated (M2) macrophage signature in the lungs, which we have previously reported to be associated with enhanced P. murina clearance. In addition, anti-P. murina class-switched Abs were increased in BL/6 Stat4(-/-) mice, but not BALB/c Stat4(-/-) mice. Supporting our experimental observations, plasma from HIV-infected individuals colonized with Pneumocystis jirovecii contained significantly lower levels of the Th2 cytokines IL-4, IL-5, and IL-13 compared with HIV-infected individuals who were not colonized. Collectively, our data suggest that robust local and systemic Th2-mediated responses are critical for immunity to Pneumocystis.
ISSN	00221767
e-ISSN	15506606
DOI	10.4049/jimmunol.1300431
Journal	The Journal of Immunology
Issue Number	12
Volume Number	190
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2013-06-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Hiv Infections Complications Pneumonia, Pneumocystis Immunology Stat4 Transcription Factor Th2 Cells Animals Cytokines Blood Enzyme-linked Immunosorbent Assay Mice Mice, Inbred Balb C Mice, Inbred C57bl Mice, Knockout Real-time Polymerase Chain Reaction Research Support, N.i.h., Extramural Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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