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Persistent and compartmentalised disruption of dendritic cell subpopulations in the lung following influenza A virus infection.

Strickland DH, Fear V, Shenton S, Wikstrom ME, Zosky G, Larcombe AN, Holt PG, Berry C, von Garnier C, Stumbles PA - PLoS ONE (2014)

Bottom Line: A significant depletion in the percentage of AMDC was observed at day 4 post-infection that was associated with a change in steady-state CD11b+ and CD11b- AMDC subset frequencies and significantly elevated CD40 and CD80 expression and that returned to baseline by day 14 post-infection.In contrast, percentages and total numbers of PLDC were significantly elevated at day 14 and remained so until day 21 post-infection.Accompanying this was a change in CD11b+and CD11b- PLDC subset frequencies and significant increase in CD40 and CD80 expression at these time points.

View Article: PubMed Central - PubMed

Affiliation: Telethon Institute for Child Health Research and Centre for Child Health Research, University of Western Australia, Perth, W.A., Australia.

ABSTRACT
Immunological homeostasis in the respiratory tract is thought to require balanced interactions between networks of dendritic cell (DC) subsets in lung microenvironments in order to regulate tolerance or immunity to inhaled antigens and pathogens. Influenza A virus (IAV) poses a serious threat of long-term disruption to this balance through its potent pro-inflammatory activities. In this study, we have used a BALB/c mouse model of A/PR8/34 H1N1 Influenza Type A Virus infection to examine the effects of IAV on respiratory tissue DC subsets during the recovery phase following clearance of the virus. In adult mice, we found differences in the kinetics and activation states of DC residing in the airway mucosa (AMDC) compared to those in the parenchymal lung (PLDC) compartments. A significant depletion in the percentage of AMDC was observed at day 4 post-infection that was associated with a change in steady-state CD11b+ and CD11b- AMDC subset frequencies and significantly elevated CD40 and CD80 expression and that returned to baseline by day 14 post-infection. In contrast, percentages and total numbers of PLDC were significantly elevated at day 14 and remained so until day 21 post-infection. Accompanying this was a change in CD11b+and CD11b- PLDC subset frequencies and significant increase in CD40 and CD80 expression at these time points. Furthermore, mice infected with IAV at 4 weeks of age showed a significant increase in total numbers of PLDC, and increased CD40 expression on both AMDC and PLDC, when analysed as adults 35 days later. These data suggest that the rate of recovery of DC populations following IAV infection differs in the mucosal and parenchymal compartments of the lung and that DC populations can remain disrupted and activated for a prolonged period following viral clearance, into adulthood if infection occurred early in life.

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Time course of changes in the expression of CD11b on respiratory DC subsets in anatomical compartments of the respiratory tract following IAV infection.(A and B) Percentage frequency of CD11blo AMDC (A) and CD11bhi AMDC (B) amongst total AMDC (gated as per Fig. 4A) in IAV infected (closed circles) and control mice (open circles). (C and D) Percentage frequency of CD11blo PLDC (A) and CD11bhi PLDC (B) amongst total PLDC (gated as per Fig. 4D) in IAV infected (closed circles) and control mice (open circles). Data are means +/− SEM for 3 independent infection experiments using pools of tissue from 3 to 4 mice for each experiment. *  =  p<0.05; **  =  p<0.01; ***  =  p<0.001.
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pone-0111520-g005: Time course of changes in the expression of CD11b on respiratory DC subsets in anatomical compartments of the respiratory tract following IAV infection.(A and B) Percentage frequency of CD11blo AMDC (A) and CD11bhi AMDC (B) amongst total AMDC (gated as per Fig. 4A) in IAV infected (closed circles) and control mice (open circles). (C and D) Percentage frequency of CD11blo PLDC (A) and CD11bhi PLDC (B) amongst total PLDC (gated as per Fig. 4D) in IAV infected (closed circles) and control mice (open circles). Data are means +/− SEM for 3 independent infection experiments using pools of tissue from 3 to 4 mice for each experiment. *  =  p<0.05; **  =  p<0.01; ***  =  p<0.001.

Mentions: In addition to anatomical location, we and others have shown that the myeloid marker CD11b functionally divides mouse lung DC, with CD11bhi and CD11blo DC subsets showing different rates of capture and trafficking of inhaled antigens in the steady-state and during allergic inflammatory airways disease [15], [16], [30]. Furthermore, the CD11blo DC subset has been shown to be important for clearance of IAV and to have distinct functional properties in terms of T cell recruitment and activation [22], [23]. In the current study, analysis of CD11b expression on respiratory tract DC populations following IAV infection showed a compartmentalised change. In the airway mucosa, IAV infection induced a significant decrease in the percentage of CD11blo AMDC (Fig. 5A), and corresponding increase in the percentage of CD11bhi AMDC (Fig. 5B) at d4 and d7 p.i., returning to control levels for each subset at d14 p.i. Similarly, IAV infection also induced a decrease in the percentage of CD11blo PLDC (Fig. 5C), and increase in the percentage of CD11bhi PLDC at d7 p.i. (Fig. 5D). However, in contrast to AMDC, changes in CD11b expression on PLDC persisted, remaining significantly changed from control PLDC until d21 p.i. (Fig. 5C and 5D).


Persistent and compartmentalised disruption of dendritic cell subpopulations in the lung following influenza A virus infection.

Strickland DH, Fear V, Shenton S, Wikstrom ME, Zosky G, Larcombe AN, Holt PG, Berry C, von Garnier C, Stumbles PA - PLoS ONE (2014)

Time course of changes in the expression of CD11b on respiratory DC subsets in anatomical compartments of the respiratory tract following IAV infection.(A and B) Percentage frequency of CD11blo AMDC (A) and CD11bhi AMDC (B) amongst total AMDC (gated as per Fig. 4A) in IAV infected (closed circles) and control mice (open circles). (C and D) Percentage frequency of CD11blo PLDC (A) and CD11bhi PLDC (B) amongst total PLDC (gated as per Fig. 4D) in IAV infected (closed circles) and control mice (open circles). Data are means +/− SEM for 3 independent infection experiments using pools of tissue from 3 to 4 mice for each experiment. *  =  p<0.05; **  =  p<0.01; ***  =  p<0.001.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4232261&req=5

pone-0111520-g005: Time course of changes in the expression of CD11b on respiratory DC subsets in anatomical compartments of the respiratory tract following IAV infection.(A and B) Percentage frequency of CD11blo AMDC (A) and CD11bhi AMDC (B) amongst total AMDC (gated as per Fig. 4A) in IAV infected (closed circles) and control mice (open circles). (C and D) Percentage frequency of CD11blo PLDC (A) and CD11bhi PLDC (B) amongst total PLDC (gated as per Fig. 4D) in IAV infected (closed circles) and control mice (open circles). Data are means +/− SEM for 3 independent infection experiments using pools of tissue from 3 to 4 mice for each experiment. *  =  p<0.05; **  =  p<0.01; ***  =  p<0.001.
Mentions: In addition to anatomical location, we and others have shown that the myeloid marker CD11b functionally divides mouse lung DC, with CD11bhi and CD11blo DC subsets showing different rates of capture and trafficking of inhaled antigens in the steady-state and during allergic inflammatory airways disease [15], [16], [30]. Furthermore, the CD11blo DC subset has been shown to be important for clearance of IAV and to have distinct functional properties in terms of T cell recruitment and activation [22], [23]. In the current study, analysis of CD11b expression on respiratory tract DC populations following IAV infection showed a compartmentalised change. In the airway mucosa, IAV infection induced a significant decrease in the percentage of CD11blo AMDC (Fig. 5A), and corresponding increase in the percentage of CD11bhi AMDC (Fig. 5B) at d4 and d7 p.i., returning to control levels for each subset at d14 p.i. Similarly, IAV infection also induced a decrease in the percentage of CD11blo PLDC (Fig. 5C), and increase in the percentage of CD11bhi PLDC at d7 p.i. (Fig. 5D). However, in contrast to AMDC, changes in CD11b expression on PLDC persisted, remaining significantly changed from control PLDC until d21 p.i. (Fig. 5C and 5D).

Bottom Line: A significant depletion in the percentage of AMDC was observed at day 4 post-infection that was associated with a change in steady-state CD11b+ and CD11b- AMDC subset frequencies and significantly elevated CD40 and CD80 expression and that returned to baseline by day 14 post-infection.In contrast, percentages and total numbers of PLDC were significantly elevated at day 14 and remained so until day 21 post-infection.Accompanying this was a change in CD11b+and CD11b- PLDC subset frequencies and significant increase in CD40 and CD80 expression at these time points.

View Article: PubMed Central - PubMed

Affiliation: Telethon Institute for Child Health Research and Centre for Child Health Research, University of Western Australia, Perth, W.A., Australia.

ABSTRACT
Immunological homeostasis in the respiratory tract is thought to require balanced interactions between networks of dendritic cell (DC) subsets in lung microenvironments in order to regulate tolerance or immunity to inhaled antigens and pathogens. Influenza A virus (IAV) poses a serious threat of long-term disruption to this balance through its potent pro-inflammatory activities. In this study, we have used a BALB/c mouse model of A/PR8/34 H1N1 Influenza Type A Virus infection to examine the effects of IAV on respiratory tissue DC subsets during the recovery phase following clearance of the virus. In adult mice, we found differences in the kinetics and activation states of DC residing in the airway mucosa (AMDC) compared to those in the parenchymal lung (PLDC) compartments. A significant depletion in the percentage of AMDC was observed at day 4 post-infection that was associated with a change in steady-state CD11b+ and CD11b- AMDC subset frequencies and significantly elevated CD40 and CD80 expression and that returned to baseline by day 14 post-infection. In contrast, percentages and total numbers of PLDC were significantly elevated at day 14 and remained so until day 21 post-infection. Accompanying this was a change in CD11b+and CD11b- PLDC subset frequencies and significant increase in CD40 and CD80 expression at these time points. Furthermore, mice infected with IAV at 4 weeks of age showed a significant increase in total numbers of PLDC, and increased CD40 expression on both AMDC and PLDC, when analysed as adults 35 days later. These data suggest that the rate of recovery of DC populations following IAV infection differs in the mucosal and parenchymal compartments of the lung and that DC populations can remain disrupted and activated for a prolonged period following viral clearance, into adulthood if infection occurred early in life.

Show MeSH
Related in: MedlinePlus