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Administration of immunobiotic Lactobacillus plantarum delays but does not prevent lethal pneumovirus infection in Rag1^-/- mice.

ABSTRACT: Administration of immunobiotic Lactobacillus plantarum (Lp) directly to the respiratory mucosa promotes cross-protection against lethal pneumovirus infection via B-cell-independent mechanisms. In this study, we examined Lp-mediated cross protection in Rag1^-/- mice which cannot clear virus from lung tissue. Although Lp was initially protective, Rag1^-/- mice ultimately succumbed to a delayed lethal outcome associated with local production of the proinflammatory cytokines CCL1, -2, and -7, granulocyte recruitment, and ongoing virus replication. By contrast, CD8^null mice, which are fully capable of clearing virus, are protected by Lp with no delayed lethal outcome, granulocyte recruitment to the airways, or induction of CCL7. Repeated administration of Lp to virus-infected Rag1^-/- mice had no impact on delayed mortality. Moreover, administration of Lp to the respiratory mucosa resulted in no induction of IFN-? or -? in Rag1^-/- or wild-type mice, and IFN-abR gene deletion had no impact on Lp-mediated protection. Overall, our findings indicate that although Lp administered to the respiratory tract has substantial impact on lethal virus-induced inflammation in situ, endogenous virus clearance mechanisms are needed to promote sustained protection. Our results suggest that a larger understanding of the mechanisms and mediators that limit acute virus-induced inflammation may yield new and useful therapeutic modalities.

SUBMITTER: Percopo CM

PROVIDER: S-EPMC5557638 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Administration of immunobiotic Lactobacillus plantarum delays but does not prevent lethal pneumovirus infection in Rag1-/- mice.

Percopo Caroline M CM Ma Michelle M Rosenberg Helene F HF

Journal of leukocyte biology 20170615 3

Administration of immunobiotic Lactobacillus plantarum (Lp) directly to the respiratory mucosa promotes cross-protection against lethal pneumovirus infection via B-cell-independent mechanisms. In this study, we examined Lp-mediated cross protection in Rag1-/- mice which cannot clear virus from lung tissue. Although Lp was initially protective, Rag1-/- mice ultimately succumbed to a delayed lethal outcome associated with local production of the proinflam ...[more]

PMID: 28619948

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Project description:UNLABELLED:Pneumonia virus of mice (PVM) is a natural rodent pathogen that replicates in bronchial epithelial cells and reproduces many clinical and pathological features of the more severe forms of disease associated with human respiratory syncytial virus. In order to track virus-target cell interactions during acute infection in vivo, we developed rK2-PVM, bacterial artificial chromosome-based recombinant PVM strain J3666 that incorporates the fluorescent tag monomeric Katushka 2 (mKATE2). The rK2-PVM pathogen promotes lethal infection in BALB/c mice and elicits characteristic cytokine production and leukocyte recruitment to the lung parenchyma. Using recombinant virus, we demonstrate for the first time PVM infection of both dendritic cells (DCs; CD11c(+) major histocompatibility complex class II(+)) and alveolar macrophages (AMs; CD11c(+) sialic acid-binding immunoglobulin-like lectin F(+)) in vivo and likewise detect mKATE2(+) DCs in mediastinal lymph nodes from infected mice. AMs support both active virus replication and production of infectious virions. Furthermore, we report that priming of the respiratory tract with immunobiotic Lactobacillus plantarum, a regimen that results in protection against the lethal inflammatory sequelae of acute respiratory virus infection, resulted in differential recruitment of neutrophils, DCs, and lymphocytes to the lungs in response to rK2-PVM and a reduction from ? 40% to <10% mKATE2(+) AMs in association with a 2-log drop in the release of infectious virions. In contrast, AMs from L. plantarum-primed mice challenged with virus ex vivo exhibited no differential susceptibility to rK2-PVM. Although the mechanisms underlying Lactobacillus-mediated viral suppression remain to be fully elucidated, this study provides insight into the cellular basis of this response. IMPORTANCE:Pneumonia virus of mice (PVM) is a natural mouse pathogen that serves as a model for severe human respiratory syncytial virus disease. We have developed a fully functional recombinant PVM strain with a fluorescent reporter protein (rK2-PVM) that permits us to track infection of target cells in vivo. With rK2-PVM, we demonstrate infection of leukocytes in the lung, notably, dendritic cells and alveolar macrophages. Alveolar macrophages undergo productive infection and release infectious virions. We have shown previously that administration of immunobiotic Lactobacillus directly to the respiratory mucosa protects mice from the lethal sequelae of PVM infection in association with profound suppression of the virus-induced inflammatory response. We show here that Lactobacillus administration also limits infection of leukocytes in vivo and results in diminished release of infectious virions from alveolar macrophages. This is the first study to provide insight into the cellular basis of the antiviral impact of immunobiotic L. plantarum.

Dataset Information

Administration of immunobiotic Lactobacillus plantarum delays but does not prevent lethal pneumovirus infection in Rag1^-/- mice.

Publications

Administration of immunobiotic <i>Lactobacillus plantarum</i> delays but does not prevent lethal pneumovirus infection in <i>Rag1</i><sup>-/-</sup> mice.

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