Lactobacillus-mediated priming of the respiratory mucosa protects against lethal pneumovirus infection.

Lactobacillus-mediated priming of the respiratory mucosa protects against lethal pneumovirus infection.
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DOI:
10.4049/jimmunol.1001751
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发表时间:
2011-01-15
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Rosenberg HF
Rosenberg HF
中科院分区:
其他
文献类型:
--
作者:
Gabryszewski SJ;Bachar O;Dyer KD;Percopo CM;Killoran KE;Domachowske JB;Rosenberg HF

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The inflammatory response to respiratory virus infection can be complex and refractory to standard therapy. Lactobacilli, when targeted to the respiratory epithelium, are highly effective at suppressing virus-induced inflammation and protecting against lethal disease. Specifically, wild-type mice primed via intranasal inoculation with live or heat-inactivated Lactobacillus plantarum or Lactobacillus reuteri were completely protected against lethal infection with the virulent rodent pathogen, pneumonia virus of mice (PVM); significant protection (60% survival) persisted for at least thirteen weeks. Protection was not unique to Lactobacillus species, and was also observed in response to priming with non-pathogenic gram-positive Listeria innocua. Priming with live lactobacilli resulted in diminished granulocyte recruitment, diminished expression of multiple proinflammatory cytokines (CXCL10, CXCL1, CCL2, and TNF) and reduced virus recovery, although we have demonstrated clearly that absolute virus titer does not predict clinical outcome. Lactobacillus priming also resulted in prolonged survival and protection against the lethal sequelae of PVM infection in MyD88 gene-deleted (MyD88−/−) mice, suggesting that the protective mechanisms may be Toll-like receptor-independent. Most intriguing, virus recovery and cytokine expression patterns in Lactobacillus-primed MyD88−/− mice were indistinguishable from those observed in control-primed MyD88−/− counterparts, In summary, we have identified and characterized an effective Lactobacillus-mediated innate immune shield, which may ultimately serve as critical and long-term protection against infection in the absence of specific antiviral vaccines.
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