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Titolo:
Role of innate and adaptive immunity in the outcome of primary infection with Chlamydia pneumoniae, as analyzed in genetically modified mice
Autore:
Rottenberg, ME; Rothfuchs, ACG; Gigliotti, D; Svanholm, C; Bandholtz, L; Wigzell, H;
Indirizzi:
Karolinska Inst, Ctr Microbiol & Tumor Biol, S-17177 Stockholm, Sweden Karolinska Inst Stockholm Sweden S-17177 Biol, S-17177 Stockholm, Sweden
Titolo Testata:
JOURNAL OF IMMUNOLOGY
fascicolo: 5, volume: 162, anno: 1999,
pagine: 2829 - 2836
SICI:
0022-1767(19990301)162:5<2829:ROIAAI>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
GENITAL-TRACT INFECTION; NITRIC-OXIDE SYNTHASE; TNF RECEPTOR P55; HELPER T-CELLS; DEFICIENT MICE; IGE RESPONSES; MYCOBACTERIUM-TUBERCULOSIS; LEISHMANIA-MAJOR; STRAIN TWAR; LACKING;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
52
Recensione:
Indirizzi per estratti:
Indirizzo: Rottenberg, ME Karolinska Inst, Ctr Microbiol & Tumor Biol, S-17177 Stockholm, Sweden Karolinska Inst Stockholm Sweden S-17177 tockholm, Sweden
Citazione:
M.E. Rottenberg et al., "Role of innate and adaptive immunity in the outcome of primary infection with Chlamydia pneumoniae, as analyzed in genetically modified mice", J IMMUNOL, 162(5), 1999, pp. 2829-2836

Abstract

Infection with Chlamydia pneumoniae is a common cause of acute respiratorydisease in man and is also associated with atherosclerotic cardiovascular disorder. Herein, we have compared bacterial load and immune parameters of C. pneumoniae-infected mice genomically lacking T cell coreceptors, cytokine receptors, or cytotoxic effector molecules. A protective role for CD8(+) cells is shown by the enhanced severity of infection of CD8(-/-) or TAP-1(-/-)/beta(2)-microglobulin(-/-) mice. CD8(+) cells hindered a parasite growth-promoting role of CD4(+) T cells, as indicated by the higher sensitivity to early infection of CD8(-/-) than CD4(-/-)/CD8(-/-) mice, which was further confirmed in experiments in which SCID mice were reconstituted with either CD4(+) or CD4(+) plus CD8(+) T cells. Interestingly, CD4(+) T cells played a dual role, detrimental early (14 and 24 days) after infection but protective at later time points (60 days after infection). The CD8(+) T cell protection was perforin independent. The early deleterious role of CD4(+) in the absence of CD8(+) T cells was associated with enhanced IL-4 and IL-10 mRNA levels and delayed IFN-gamma mRNA accumulation in lungs. In line with this, IFN-gamma R-/- (but not TNFRp55(-/-)) mice showed dramatically increased susceptibility to C. pneumoniae, linked to reduced inducible nitric oxide synthase (iNOS) mRNA accumulation, but not to diminished levels of specific Abs, The increased susceptibility of iNOS(-/-) mice indicates a protective role for iNOS activity during infection with C. pneumoniae, The higher sensitivity of IFN-gamma R-/- mice to C, pneumoniae compared with that of SCID or recombination-activating gene-1(-/-) mice suggested a relevant protective role of IFN-gamma-dependent innate mechanisms of protection.

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Documento generato il 24/09/20 alle ore 05:01:30