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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

Lung function in IL-12p40-KO mice infected with hMPV.WT or IL-12p40-KO mice were infected with hMPV (5×106 PFU/mice), and airway resistance was measured at day 15 after hMPV infection. Change in airway resistance between baseline values after challenge with different concentrations of aerosolized methacholine (0.1, 1, 10, 25, and 50 mg/ml) was measured by the Flexivent system (Resistance units = cmH2O.s/mL). Values represent mean ± SEM. n = 4 mice/group. *P<0.05.
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pone-0037173-g006: Lung function in IL-12p40-KO mice infected with hMPV.WT or IL-12p40-KO mice were infected with hMPV (5×106 PFU/mice), and airway resistance was measured at day 15 after hMPV infection. Change in airway resistance between baseline values after challenge with different concentrations of aerosolized methacholine (0.1, 1, 10, 25, and 50 mg/ml) was measured by the Flexivent system (Resistance units = cmH2O.s/mL). Values represent mean ± SEM. n = 4 mice/group. *P<0.05.

Mentions: To assess the role of IL-12p40 on pulmonary function after hMPV infection, WT and IL-12p40-KO mice were infected with hMPV (or mock infected as baseline control) and then invasive assessment of lung function 15 days later was conducted. No differences in lung resistance were observed between the WT and IL-12p40-KO groups at concentrations of methacholine of 0.1 and 1.0. However, administration of higher concentrations of methacholine revealed significant functional changes in IL-12p40-KO mice. When compared to WT, deficient animals showed over a two-fold increase of lung resistance at doses of 10, 25, and 50 mg/ml of methacholine. That difference was increased one more fold when compared to mock-infected groups (Fig. 6).


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)

Lung function in IL-12p40-KO mice infected with hMPV.WT or IL-12p40-KO mice were infected with hMPV (5×106 PFU/mice), and airway resistance was measured at day 15 after hMPV infection. Change in airway resistance between baseline values after challenge with different concentrations of aerosolized methacholine (0.1, 1, 10, 25, and 50 mg/ml) was measured by the Flexivent system (Resistance units = cmH2O.s/mL). Values represent mean ± SEM. n = 4 mice/group. *P<0.05.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0037173-g006: Lung function in IL-12p40-KO mice infected with hMPV.WT or IL-12p40-KO mice were infected with hMPV (5×106 PFU/mice), and airway resistance was measured at day 15 after hMPV infection. Change in airway resistance between baseline values after challenge with different concentrations of aerosolized methacholine (0.1, 1, 10, 25, and 50 mg/ml) was measured by the Flexivent system (Resistance units = cmH2O.s/mL). Values represent mean ± SEM. n = 4 mice/group. *P<0.05.
Mentions: To assess the role of IL-12p40 on pulmonary function after hMPV infection, WT and IL-12p40-KO mice were infected with hMPV (or mock infected as baseline control) and then invasive assessment of lung function 15 days later was conducted. No differences in lung resistance were observed between the WT and IL-12p40-KO groups at concentrations of methacholine of 0.1 and 1.0. However, administration of higher concentrations of methacholine revealed significant functional changes in IL-12p40-KO mice. When compared to WT, deficient animals showed over a two-fold increase of lung resistance at doses of 10, 25, and 50 mg/ml of methacholine. That difference was increased one more fold when compared to mock-infected groups (Fig. 6).

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