Severe sepsis exacerbates cell-mediated immunity in the lung due to an altered dendritic cell cytokine profile

Haitao Wen, Cory M. Hogaboam, Jack Gauldie, Steven L. Kunkel

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Severe sepsis leads to long-term alterations in the immune response of surviving individuals. We have modeled this alteration in host immunity by studying the survivors of severe experimental sepsis (murine cecal ligation and puncture), which were subsequently challenged with lung granuloma-inducing Schistosoma mansoni eggs. This granulomatous response is a well-studied cell-mediated immune reaction characterized by elevated levels of type-2 cytokines. Pulmonary granulomas induced by S. mansoni eggs in cecal ligation and puncture survivors were significantly larger and contained more eosinophils than granulomas in sham-operated mice. Significantly lower interleukin (IL)-12p40 mRNA and IL-12p70 protein levels were observed in the lungs of postseptic mice with developing granulomas, compared with controls. Postseptic mice had significantly fewer dendritic cells in the lungs during the granulomatous response. Isolated lung dendritic cells from postseptic mice at days 8 and 16 after S. mansoni egg challenge exhibited defective IL-12 synthesis but enhanced IL-10 synthesis after Toll-like receptor agonist challenge. Pulmonary transfection with an IL-12-expressing adenovirus in postseptic mice reversed the skewing of the pulmonary cytokine profile and normalized the lung granulomatous response. Our data indicate that severe sepsis shifts the pulmonary cytokine environment, presumably via effects on pulmonary dendritic cells, which in turn alters the lung cell-mediated immune response.

Original languageEnglish (US)
Pages (from-to)1940-1950
Number of pages11
JournalAmerican Journal of Pathology
Volume168
Issue number6
DOIs
StatePublished - Jun 2006

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Cellular Immunity
Dendritic Cells
Sepsis
Cytokines
Lung
Granuloma
Schistosoma mansoni
Interleukins
Interleukin-12
Punctures
Eggs
Ligation
Toll-Like Receptors
Eosinophils
Adenoviridae
Interleukin-10
Transfection
Ovum
Immunity
Messenger RNA

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Severe sepsis exacerbates cell-mediated immunity in the lung due to an altered dendritic cell cytokine profile. / Wen, Haitao; Hogaboam, Cory M.; Gauldie, Jack; Kunkel, Steven L.

In: American Journal of Pathology, Vol. 168, No. 6, 06.2006, p. 1940-1950.

Research output: Contribution to journalArticle

Wen, Haitao ; Hogaboam, Cory M. ; Gauldie, Jack ; Kunkel, Steven L. / Severe sepsis exacerbates cell-mediated immunity in the lung due to an altered dendritic cell cytokine profile. In: American Journal of Pathology. 2006 ; Vol. 168, No. 6. pp. 1940-1950.
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