Limits...
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.

Show MeSH

Related in: MedlinePlus

Pulmonary inflammation in hMPV-infected IL-12p40-KO mice.C57BL/6 and IL-12p40-KO mice were infected i.n. with 5×106 PFU of hMPV or mock-treated and lungs were harvested at day 7 after hMPV infection, fixed for slide preparation and H&E stained. (A) Representative stained lung tissue sections from the indicated treatment. Arrows indicate cells infiltrating the perivascular and peribronchial spaces, Scale bar = 200 µm. (B) Pathology score of prepared slides (scored as described in Materials and Methods). n = 5 mice/group. **P<0.01.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3351396&req=5

pone-0037173-g002: Pulmonary inflammation in hMPV-infected IL-12p40-KO mice.C57BL/6 and IL-12p40-KO mice were infected i.n. with 5×106 PFU of hMPV or mock-treated and lungs were harvested at day 7 after hMPV infection, fixed for slide preparation and H&E stained. (A) Representative stained lung tissue sections from the indicated treatment. Arrows indicate cells infiltrating the perivascular and peribronchial spaces, Scale bar = 200 µm. (B) Pathology score of prepared slides (scored as described in Materials and Methods). n = 5 mice/group. **P<0.01.

Mentions: Next, we determined the role of IL-12p40 in the regulation of lung inflammation in response to hMPV infection. Pathology score and differential cell count in BAL fluid were assessed in WT and IL-12p40-KO mice. Groups of animals were infected i.n. with 5×106 PFU of hMPV and lung tissue and BAL fluid were harvested at day 7 after infection (when pulmonary inflammation peaks [33]). Lung sections were processed and stained by Hematoxylin and eosin (H&E) and cells from BAL samples were counted, cytospun and analyzed for differential cell analysis. Lung histopathology analysis demonstrated that no airway inflammation was observed in mock-infected WT or KO mice (Fig. 2A, upper panels). However, hMPV infection induced a cellular infiltration in the perivascular and peribronchial spaces of WT mice (Fig. 2A, lower left panel) which was exacerbated in the absence of IL-12p40 (Fig. 2A, lower right panel). Quantification of the pulmonary inflammation, represented as pathology score, indicated that the inflammation in the respiratory tract of IL-12p40-KO mice was increased over two-fold when compared to WT animals (Fig. 2B).


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)

Pulmonary inflammation in hMPV-infected IL-12p40-KO mice.C57BL/6 and IL-12p40-KO mice were infected i.n. with 5×106 PFU of hMPV or mock-treated and lungs were harvested at day 7 after hMPV infection, fixed for slide preparation and H&E stained. (A) Representative stained lung tissue sections from the indicated treatment. Arrows indicate cells infiltrating the perivascular and peribronchial spaces, Scale bar = 200 µm. (B) Pathology score of prepared slides (scored as described in Materials and Methods). n = 5 mice/group. **P<0.01.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0037173-g002: Pulmonary inflammation in hMPV-infected IL-12p40-KO mice.C57BL/6 and IL-12p40-KO mice were infected i.n. with 5×106 PFU of hMPV or mock-treated and lungs were harvested at day 7 after hMPV infection, fixed for slide preparation and H&E stained. (A) Representative stained lung tissue sections from the indicated treatment. Arrows indicate cells infiltrating the perivascular and peribronchial spaces, Scale bar = 200 µm. (B) Pathology score of prepared slides (scored as described in Materials and Methods). n = 5 mice/group. **P<0.01.
Mentions: Next, we determined the role of IL-12p40 in the regulation of lung inflammation in response to hMPV infection. Pathology score and differential cell count in BAL fluid were assessed in WT and IL-12p40-KO mice. Groups of animals were infected i.n. with 5×106 PFU of hMPV and lung tissue and BAL fluid were harvested at day 7 after infection (when pulmonary inflammation peaks [33]). Lung sections were processed and stained by Hematoxylin and eosin (H&E) and cells from BAL samples were counted, cytospun and analyzed for differential cell analysis. Lung histopathology analysis demonstrated that no airway inflammation was observed in mock-infected WT or KO mice (Fig. 2A, upper panels). However, hMPV infection induced a cellular infiltration in the perivascular and peribronchial spaces of WT mice (Fig. 2A, lower left panel) which was exacerbated in the absence of IL-12p40 (Fig. 2A, lower right panel). Quantification of the pulmonary inflammation, represented as pathology score, indicated that the inflammation in the respiratory tract of IL-12p40-KO mice was increased over two-fold when compared to WT animals (Fig. 2B).

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