In vivo regulation of replicative Legionella pneumophila lung infection by endogenous interleukin-12.

Abstract:

:The in vivo role of endogenous interleukin 12 (IL-12) in modulating intrapulmonary growth of Legionella pneumophila was assessed by using a murine model of replicative L. pneumophila lung infection. Intratracheal inoculation of A/J mice with virulent bacteria (10(6) L. pneumophila cells per mouse) resulted in induction of IL-12, which preceded clearance of the bacteria from the lung. Inhibition of endogenous IL-12 activity, via administration of IL-12 neutralizing antiserum, resulted in enhanced intrapulmonary growth of the bacteria within 5 days postinfection (compared to untreated L. pneumophila-infected mice). Because IL-12 has previously been shown to modulate the expression of cytokines, including gamma interferon (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), and IL-10, which regulate L. pneumophila growth, immunomodulatory effects of endogenous IL-12 on intrapulmonary levels of these cytokines during replicative L. pneumophila lung infection were subsequently assessed. Results of these experiments demonstrated that TNF-alpha activity was significantly lower, while protein levels of IFN-gamma and IL-10 in the lung were similar, in L. pneumophila-infected mice administered IL-12 antiserum, compared to similarly infected untreated mice. Together, these results demonstrate that IL-12 is critical for resolution of replicative L. pneumophila lung infection and suggest that regulation of intrapulmonary growth of L. pneumophila by endogenous IL-12 is mediated, at least in part, by TNF-alpha.

journal_name

Infect Immun

journal_title

Infection and immunity

authors

Brieland JK,Remick DG,LeGendre ML,Engleberg NC,Fantone JC

doi

10.1128/IAI.66.1.65-69.1998

subject

Has Abstract

pub_date

1998-01-01 00:00:00

pages

65-9

issue

1

eissn

0019-9567

issn

1098-5522

journal_volume

66

pub_type

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