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Interleukin-12p40 modulates human metapneumovirus-induced pulmonary disease in an acute mouse model of infection.

Chakraborty K, Zhou Z, Wakamatsu N, Guerrero-Plata A - PLoS ONE (2012)

Bottom Line: IL-12p40, a known important mediator in limiting lung inflammation, is induced by hMPV and its production is sustained after the resolution phase of infection suggesting that this cytokine plays a role in the immune response against hMPV.However, hMPV infection in these mice does not have an effect on viral replication.These results identify an important regulatory role of IL-12p40 in hMPV infection.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathobiological Sciences, Louisiana State University, Baton Rouge, Louisiana, United States of America.

ABSTRACT
The mechanisms that regulate the host immune response induced by human metapneumovirus (hMPV), a newly-recognized member of the Paramyxoviridae family, are largely unknown. Cytokines play an important role in modulating inflammatory responses during viral infections. IL-12p40, a known important mediator in limiting lung inflammation, is induced by hMPV and its production is sustained after the resolution phase of infection suggesting that this cytokine plays a role in the immune response against hMPV. In this work, we demonstrated that in mice deficient in IL-12p40, hMPV infection induced an exacerbated pulmonary inflammatory response and mucus production, altered cytokine response, and decreased lung function. However, hMPV infection in these mice does not have an effect on viral replication. These results identify an important regulatory role of IL-12p40 in hMPV infection.

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Related in: MedlinePlus

Cytokine and chemokine production in the lung of IL-12p40-KO mice infected with hMPV.WT and IL-12p40-KO mice were infected i.n. with 5×106 PFU of hMPV or mock-infected and sacrificed at day 7 after infection. BAL samples were collected from each group of mice and assessed for cytokine/chemokine production by a multi-Plex Cytokine detection system. n = 7–8 mice/group.*P<0.05.
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pone-0037173-g005: Cytokine and chemokine production in the lung of IL-12p40-KO mice infected with hMPV.WT and IL-12p40-KO mice were infected i.n. with 5×106 PFU of hMPV or mock-infected and sacrificed at day 7 after infection. BAL samples were collected from each group of mice and assessed for cytokine/chemokine production by a multi-Plex Cytokine detection system. n = 7–8 mice/group.*P<0.05.

Mentions: To define the role of IL-12p40 in the regulation of hMPV-induced cytokine response, the level of cytokines and chemokines was assessed in IL-12p40-KO mice and compared to WT ones. Mice were infected i.n. with hMPV, and at day 7 after infection, BAL samples were collected from each group of mice and assessed for the presence of cytokines by using a multi-plex cytokine detection system. Our data indicate that, compared to immunocompetent mice, the lack of IL-12p40 significantly decreased the production of the Th1 regulatory cytokine IFN-γ and the proinflammatory cytokine IL-6 by 65% and 82%, respectively (Fig. 5). A similar effect was observed with the release of the chemokines CXCL10 (IP-10) and CCL2 (MCP-1), where their production was decreased by over 60% in both cases. On the other hand, the production of CCL11 (Eotaxin) and CXCL1 (KC, IL-8 homologue), cytokines that regulates the chemotaxis and function of neutrophils and eosinophils, was upregulated in the absence of IL-12p40. Expression of CCL11 and CXCL1 was increased over two times in the deficient mice in response to hMPV infection when compared to WT mice. Finally, production of CXCL2 (MIP-2), CCL4 (MIP-1β), CCL3 (MIP-1α), and CXCL9 (MIG) was induced after hMPV infection but no changes were observed in IL-12p40-KO vs WT mice (not shown). Overall, these data indicate that IL-12p40 regulates the cytokine response in hMPV infected mice.


Interleukin-12p40 modulates human metapneumovirus-induced pulmonary disease in an acute mouse model of infection.

Chakraborty K, Zhou Z, Wakamatsu N, Guerrero-Plata A - PLoS ONE (2012)

Cytokine and chemokine production in the lung of IL-12p40-KO mice infected with hMPV.WT and IL-12p40-KO mice were infected i.n. with 5×106 PFU of hMPV or mock-infected and sacrificed at day 7 after infection. BAL samples were collected from each group of mice and assessed for cytokine/chemokine production by a multi-Plex Cytokine detection system. n = 7–8 mice/group.*P<0.05.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3351396&req=5

pone-0037173-g005: Cytokine and chemokine production in the lung of IL-12p40-KO mice infected with hMPV.WT and IL-12p40-KO mice were infected i.n. with 5×106 PFU of hMPV or mock-infected and sacrificed at day 7 after infection. BAL samples were collected from each group of mice and assessed for cytokine/chemokine production by a multi-Plex Cytokine detection system. n = 7–8 mice/group.*P<0.05.
Mentions: To define the role of IL-12p40 in the regulation of hMPV-induced cytokine response, the level of cytokines and chemokines was assessed in IL-12p40-KO mice and compared to WT ones. Mice were infected i.n. with hMPV, and at day 7 after infection, BAL samples were collected from each group of mice and assessed for the presence of cytokines by using a multi-plex cytokine detection system. Our data indicate that, compared to immunocompetent mice, the lack of IL-12p40 significantly decreased the production of the Th1 regulatory cytokine IFN-γ and the proinflammatory cytokine IL-6 by 65% and 82%, respectively (Fig. 5). A similar effect was observed with the release of the chemokines CXCL10 (IP-10) and CCL2 (MCP-1), where their production was decreased by over 60% in both cases. On the other hand, the production of CCL11 (Eotaxin) and CXCL1 (KC, IL-8 homologue), cytokines that regulates the chemotaxis and function of neutrophils and eosinophils, was upregulated in the absence of IL-12p40. Expression of CCL11 and CXCL1 was increased over two times in the deficient mice in response to hMPV infection when compared to WT mice. Finally, production of CXCL2 (MIP-2), CCL4 (MIP-1β), CCL3 (MIP-1α), and CXCL9 (MIG) was induced after hMPV infection but no changes were observed in IL-12p40-KO vs WT mice (not shown). Overall, these data indicate that IL-12p40 regulates the cytokine response in hMPV infected mice.

Bottom Line: IL-12p40, a known important mediator in limiting lung inflammation, is induced by hMPV and its production is sustained after the resolution phase of infection suggesting that this cytokine plays a role in the immune response against hMPV.However, hMPV infection in these mice does not have an effect on viral replication.These results identify an important regulatory role of IL-12p40 in hMPV infection.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathobiological Sciences, Louisiana State University, Baton Rouge, Louisiana, United States of America.

ABSTRACT
The mechanisms that regulate the host immune response induced by human metapneumovirus (hMPV), a newly-recognized member of the Paramyxoviridae family, are largely unknown. Cytokines play an important role in modulating inflammatory responses during viral infections. IL-12p40, a known important mediator in limiting lung inflammation, is induced by hMPV and its production is sustained after the resolution phase of infection suggesting that this cytokine plays a role in the immune response against hMPV. In this work, we demonstrated that in mice deficient in IL-12p40, hMPV infection induced an exacerbated pulmonary inflammatory response and mucus production, altered cytokine response, and decreased lung function. However, hMPV infection in these mice does not have an effect on viral replication. These results identify an important regulatory role of IL-12p40 in hMPV infection.

Show MeSH
Related in: MedlinePlus