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 Chen, Q. Articles by Snapper, C. M. Search for Related Content PubMed PubMed Citation Articles by Chen, Q. Articles by Snapper, C. M.

Endogenous IL-1R1 Signaling Is Critical for Cognate CD4⁺ T Cell Help for Induction of In Vivo Type 1 and Type 2 Antipolysaccharide and Antiprotein Ig Isotype Responses to Intact Streptococcus pneumoniae, but Not to a Soluble Pneumococcal Conjugate Vaccine^1,2

Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814

MyD88^–/– mice exhibit defective innate, diminished CD4⁺ T cell-dependent (TD) type 1, but enhanced type 2, humoral immunity in response to intact Streptococcus pneumoniae (Pn). Because type 1 IL-1R (IL-1R1) signaling is MyD88 dependent, a role for endogenous IL-1 was determined. IL-1R1^–/–, in contrast to MyD88^–/–, mice exhibited relatively intact innate splenic cytokine expression in response to Pn. Nevertheless, IL-1R1^–/–, like MyD88^–/–, mice were more sensitive to killing with live Pn relative to wild-type controls. Although IL-1R1^–/– mice elicited a normal T cell-independent IgM antipolysaccharide (PS) response to heat-killed Pn, the induction of PS- and protein-specific cognate, but not noncognate, TD type 1 and type 2 IgG isotypes were markedly reduced. Additionally, CD4⁺ T cells from Pn-primed IL-1R1^–/– mice failed to elicit IFN-, IL-5, or IL-13 secretion upon restimulation with Pn in vitro, whereas MyD88^–/– mice secreted normal levels of IFN- and enhanced levels of IL-5 and IL-13. In contrast, IgG responses to a soluble, pneumococcal protein-PS conjugate, with or without adjuvant, showed little dependence on IL-1R1 and normal CD4⁺ T cell priming. These data are the first to demonstrate a nonredundant role for endogenous IL-1 in TD induction of humoral immune responses to an intact pathogen, although not a pathogen-derived soluble conjugate, suggesting that antigenic context is a key determinant for IL-1 dependence. These data further suggest that IL-1 may be critical for preserving CD4⁺ Th2 function in the presence, but not absence, of MyD88-dependent signaling via TLRs.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This study was supported by National Institutes of Health Grant 1R01 AI49192 and the Uniformed Services University of the Health Sciences Dean’s Research and Education Endowment Fund.

² Opinions and assertions contained herein are the private ones of the authors and are not to be construed as official or reflecting the views of Department of Defense or the Uniformed Services University of the Health Sciences.

³ Address correspondence and reprint requests to Dr. Clifford M. Snapper, Department of Pathology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814-4799. E-mail address: csnapper{at}usuhs.mil

⁴ Abbreviations used in this paper: DC, dendritic cell; Pn, intact Streptococcus pneumoniae; TI, T cell independent; PC, phosphorylcholine; C-PS, C-polysaccharide; PPS14, purified pneumococcal capsular polysaccharide, type 14; PspA, pneumococcal surface protein A; TD, T cell dependent; PC-KLH, PC-keyhole limpet hemocyanin; SN, supernatant; CpG-ODN, CpG-containing oligodeoxynucleotide; PnP, purified Pn14 protein extract; IRBP, interphotoreceptor retinoid-binding protein.

This article has been cited by other articles:

				S. Vasilevsky, J. Colino, R. Puliaev, D. H. Canaday, and C. M. Snapper Macrophages Pulsed with Streptococcus pneumoniae Elicit a T Cell-Dependent Antibody Response upon Transfer into Naive Mice J. Immunol., August 1, 2008; 181(3): 1787 - 1797. [Abstract] [Full Text] [PDF]

				G. Chattopadhyay, A. Q. Khan, G. Sen, J. Colino, W. duBois, A. Rubtsov, R. M. Torres, M. Potter, and C. M. Snapper Transgenic Expression of Bcl-xL or Bcl-2 by Murine B Cells Enhances the In Vivo Antipolysaccharide, but Not Antiprotein, Response to Intact Streptococcus pneumoniae J. Immunol., December 1, 2007; 179(11): 7523 - 7534. [Abstract] [Full Text] [PDF]

				D. A. Rao, K. J. Tracey, and J. S. Pober IL-1{alpha} and IL-1beta Are Endogenous Mediators Linking Cell Injury to the Adaptive Alloimmune Response J. Immunol., November 15, 2007; 179(10): 6536 - 6546. [Abstract] [Full Text] [PDF]

				H. M. Guay, T. A. Andreyeva, R. L. Garcea, R. M. Welsh, and E. Szomolanyi-Tsuda MyD88 Is Required for the Formation of Long-Term Humoral Immunity to Virus Infection J. Immunol., April 15, 2007; 178(8): 5124 - 5131. [Abstract] [Full Text] [PDF]