NDLI: Maximal adjuvant activity of nasally delivered IL-1 requires adjuvant-responsive CD11c(+) cells and does not correlate with adjuvant-induced in vivo cytokine production.

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Maximal adjuvant activity of nasally delivered IL-1 requires adjuvant-responsive CD11c(+) cells and does not correlate with adjuvant-induced in vivo cytokine production.

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Maximal adjuvant activity of nasally delivered IL-1 requires adjuvant-responsive CD11c(+) cells and does not correlate with adjuvant-induced in vivo cytokine production.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Johnson, Brandi T. Sempowski, Gregory D. Gunn, Michael D. DeFranco, Anthony L. Staats, Herman F. Thompson, Afton L. Hou, Baidong
Description	Country affiliation: United States Author Affiliation: Thompson AL ( Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA.)
Abstract	IL-1 has been shown to have strong mucosal adjuvant activities, but little is known about its mechanism of action. We vaccinated IL-1R1 bone marrow (BM) chimeric mice to determine whether IL-1R1 expression on stromal cells or hematopoietic cells was sufficient for the maximal adjuvant activity of nasally delivered IL-1 as determined by the acute induction of cytokine responses and induction of Bacillus anthracis lethal factor (LF)-specific adaptive immunity. Cytokine and chemokine responses induced by vaccination with IL-1 were predominantly derived from the stromal cell compartment and included G-CSF, IL-6, IL-13, MCP-1, and keratinocyte chemoattractant. Nasal vaccination of Il1r1(-/-) (knock-out [KO]) mice given wild-type (WT) BM (WTâ KO) and WTâ WT mice with LF + IL-1 induced maximal adaptive immune responses, whereas vaccination of WT mice given Il1r1(-/-) BM (KOâ WT) resulted in significantly decreased production of LF-specific serum IgG, IgG subclasses, lethal toxin-neutralizing Abs, and mucosal IgA compared with WTâ KO and WTâ WT mice (p < 0.05). IL-1 adjuvant activity was not dependent on mast cells. However, the ability of IL-1 to induce serum LF-specific IgG2c and lethal toxin-neutralizing Abs was significantly impaired in CD11c-Myd88(-/-) mice when compared with WT mice (p < 0.05). Our results suggest that CD11c(+) cells must be directly activated by nasally administered IL-1 for maximal adjuvant activity and that, although stromal cells are required for maximal adjuvant-induced cytokine production, the adjuvant-induced stromal cell cytokine responses are not required for effective induction of adaptive immunity.
ISSN	00221767
e-ISSN	15506606
DOI	10.4049/jimmunol.1100254
Journal	The Journal of Immunology
Issue Number	6
Volume Number	188
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2012-03-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Adjuvants, Immunologic Administration & Dosage Cytokines Biosynthesis Immunity, Mucosal Immunology Interleukin-1alpha Vaccination Animals Antigens, Bacterial Antigens, Cd11c Metabolism Bacterial Toxins Cell Separation Enzyme-linked Immunosorbent Assay Flow Cytometry Mice Mice, Inbred C57bl Mice, Knockout Monocytes Radiation Chimera Research Support, N.i.h., Extramural Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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