Lipopolysaccharides from distinct pathogens induce different classes of immune responses in vivo

B. Pulendran, P. Kumar, Christopher W Cutler, M. Mohamadzadeh, T. Van Dyke, J. Banchereau

Research output: Contribution to journalArticle

392 Citations (Scopus)

Abstract

The adaptive immune system has evolved distinct responses against different pathogens, but the mechanism(s) by which a particular response is initiated is poorly understood. In this study, we investigated the type of Ag-specific CD4+ Th and CD8+ T cell responses elicited in vivo, in response to soluble OVA, coinjected with LPS from two different pathogens. We used Escherichia coli LPS, which signals through Toll-like receptor 4 (TLR4) and LPS from the oral pathogen Porphyromonas gingivalis, which does not appear to require TLR4 for signaling. Coinjections of E. coli LPS + OVA or P. gingivalis LPS + OVA induced similar clonal expansions of OVA-specific CD4+ and CD8+ T cells, but strikingly different cytokine profiles. E. coli LPS induced a Th1-like response with abundant IFN-γ, but little or no IL-4, IL-13, and IL-5. In contrast, P. gingivalis LPS induced Th and T cell responses characterized by significant levels of IL-13, IL-5, and IL-10, but lower levels of IFN-γ. Consistent with these results, E. coli LPS induced IL-12(p70) in the CD8α+ dendritic cell (DC) subset, while P. gingivalis LPS did not. Both LPS, however, activated the two DC subsets to up-regulate costimulatory molecules and produce IL-6 and TNF-α. Interestingly, these LPS appeared to have differences in their ability to signal through TLR4; proliferation of splenocytes and cytokine secretion by splenocytes or DCs from TLR4-deficient C3H/HeJ mice were greatly impaired in response to E. coli LPS, but not P. gingivalis LPS. Therefore, LPS from different bacteria activate DC subsets to produce different cytokines, and induce distinct types of adaptive immunity in vivo.

Original languageEnglish (US)
Pages (from-to)5067-5076
Number of pages10
JournalJournal of Immunology
Volume167
Issue number9
DOIs
StatePublished - Nov 1 2001
Externally publishedYes

Fingerprint

Porphyromonas gingivalis
Toll-Like Receptor 4
Lipopolysaccharides
Escherichia coli
Dendritic Cells
Interleukin-13
Interleukin-5
Cytokines
T-Lymphocytes
Inbred C3H Mouse
Adaptive Immunity
Interleukin-12
Interleukin-4
Interleukin-10
Immune System
Interleukin-6
Up-Regulation
Bacteria

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Lipopolysaccharides from distinct pathogens induce different classes of immune responses in vivo. / Pulendran, B.; Kumar, P.; Cutler, Christopher W; Mohamadzadeh, M.; Van Dyke, T.; Banchereau, J.

In: Journal of Immunology, Vol. 167, No. 9, 01.11.2001, p. 5067-5076.

Research output: Contribution to journalArticle

Pulendran, B. ; Kumar, P. ; Cutler, Christopher W ; Mohamadzadeh, M. ; Van Dyke, T. ; Banchereau, J. / Lipopolysaccharides from distinct pathogens induce different classes of immune responses in vivo. In: Journal of Immunology. 2001 ; Vol. 167, No. 9. pp. 5067-5076.
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