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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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Total differential cell counts in hMPV-infected IL-12p40-KO mice.C57BL/6 and IL-12p40-KO mice were infected i.n. with 5×106 PFU of hMPV and BAL samples were harvested at day 7 after hMPV infection. Cell preparations were stained (Wright-Giemsa) and counted under the microscope (200 cells/slide). Bar graph represents mean ± SEM. n = 9 mice/group. *P<0.05, **P<0.01. (B) Representative stained cytospin preparations from the indicated treatment. Arrows indicate neutrophils infiltrating the alveolar spaces.
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pone-0037173-g003: Total differential cell counts in hMPV-infected IL-12p40-KO mice.C57BL/6 and IL-12p40-KO mice were infected i.n. with 5×106 PFU of hMPV and BAL samples were harvested at day 7 after hMPV infection. Cell preparations were stained (Wright-Giemsa) and counted under the microscope (200 cells/slide). Bar graph represents mean ± SEM. n = 9 mice/group. *P<0.05, **P<0.01. (B) Representative stained cytospin preparations from the indicated treatment. Arrows indicate neutrophils infiltrating the alveolar spaces.

Mentions: The effect of IL-12p40 on pulmonary inflammation was confirmed by the analysis of the cell populations in BAL samples. As shown in Fig. 3A, the total number of macrophages, neutrophils, and lymphocytes was increased after hMPV infection. Moreover, in the absence of IL-12p40, the number of macrophages and neutrophils was significantly increased in the BAL samples from IL-12p40-KO mice infected with hMPV as compared with that of WT hMPV-infected. In particular, an exacerbated increase in BAL neutrophils was noted in IL-12p40-KO (2.3×105±0.2) vs WT (0.7×105±0.05) hMPV-infected mice. Numbers of lymphocytes were increased after hMPV infection, but no significant difference was observed when WT and KO groups of mice were compared. No eosinophils were observed in the BAL samples of any of the groups of mice analyzed. Alveolar macrophages were mostly recovered from samples of mock-infected mice in both groups of animals (Fig. 3B, upper panels). After hMPV infection, an increased frequency of lymphocytes and neutrophils was observed. As shown in Fig. 3B (lower panels), the frequency of neutrophils in the alveolar spaces was further exacerbated in the absence of IL-12p40.


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)

Total differential cell counts in hMPV-infected IL-12p40-KO mice.C57BL/6 and IL-12p40-KO mice were infected i.n. with 5×106 PFU of hMPV and BAL samples were harvested at day 7 after hMPV infection. Cell preparations were stained (Wright-Giemsa) and counted under the microscope (200 cells/slide). Bar graph represents mean ± SEM. n = 9 mice/group. *P<0.05, **P<0.01. (B) Representative stained cytospin preparations from the indicated treatment. Arrows indicate neutrophils infiltrating the alveolar spaces.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0037173-g003: Total differential cell counts in hMPV-infected IL-12p40-KO mice.C57BL/6 and IL-12p40-KO mice were infected i.n. with 5×106 PFU of hMPV and BAL samples were harvested at day 7 after hMPV infection. Cell preparations were stained (Wright-Giemsa) and counted under the microscope (200 cells/slide). Bar graph represents mean ± SEM. n = 9 mice/group. *P<0.05, **P<0.01. (B) Representative stained cytospin preparations from the indicated treatment. Arrows indicate neutrophils infiltrating the alveolar spaces.
Mentions: The effect of IL-12p40 on pulmonary inflammation was confirmed by the analysis of the cell populations in BAL samples. As shown in Fig. 3A, the total number of macrophages, neutrophils, and lymphocytes was increased after hMPV infection. Moreover, in the absence of IL-12p40, the number of macrophages and neutrophils was significantly increased in the BAL samples from IL-12p40-KO mice infected with hMPV as compared with that of WT hMPV-infected. In particular, an exacerbated increase in BAL neutrophils was noted in IL-12p40-KO (2.3×105±0.2) vs WT (0.7×105±0.05) hMPV-infected mice. Numbers of lymphocytes were increased after hMPV infection, but no significant difference was observed when WT and KO groups of mice were compared. No eosinophils were observed in the BAL samples of any of the groups of mice analyzed. Alveolar macrophages were mostly recovered from samples of mock-infected mice in both groups of animals (Fig. 3B, upper panels). After hMPV infection, an increased frequency of lymphocytes and neutrophils was observed. As shown in Fig. 3B (lower panels), the frequency of neutrophils in the alveolar spaces was further exacerbated in the absence of IL-12p40.

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