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Exercise Improves Host Response to Influenza Viral Infection in Obese and Non-Obese Mice through Different Mechanisms.

Warren KJ, Olson MM, Thompson NJ, Cahill ML, Wyatt TA, Yoon KJ, Loiacono CM, Kohut ML - PLoS ONE (2015)

Bottom Line: Obesity has been associated with greater severity of influenza virus infection and impaired host defense.Exercise reversed the obesity-associated delay in bronchoalveolar-lavage (BAL) cell infiltration, restored BAL cytokine and chemokine production, and increased ciliary beat frequency and IFNα-related gene expression.In contrast, in non-obese mice exercise treatment results in an early reduction in lung viral load and limited inflammatory response.

View Article: PubMed Central - PubMed

Affiliation: Immunobiology Program, Iowa State University, Ames, IA, United States of America.

ABSTRACT
Obesity has been associated with greater severity of influenza virus infection and impaired host defense. Exercise may confer health benefits even when weight loss is not achieved, but it has not been determined if regular exercise improves immune defense against influenza A virus (IAV) in the obese condition. In this study, diet-induced obese mice and lean control mice exercised for eight weeks followed by influenza viral infection. Exercise reduced disease severity in both obese and non-obese mice, but the mechanisms differed. Exercise reversed the obesity-associated delay in bronchoalveolar-lavage (BAL) cell infiltration, restored BAL cytokine and chemokine production, and increased ciliary beat frequency and IFNα-related gene expression. In non-obese mice, exercise treatment reduced lung viral load, increased Type-I-IFN-related gene expression early during infection, but reduced BAL inflammatory cytokines and chemokines. In both obese and non-obese mice, exercise increased serum anti-influenza virus specific IgG2c antibody, increased CD8+ T cell percentage in BAL, and reduced TNFα by influenza viral NP-peptide-responding CD8+ T cells. Overall, the results suggest that exercise "restores" the immune response of obese mice to a phenotype similar to non-obese mice by improving the delay in immune activation. In contrast, in non-obese mice exercise treatment results in an early reduction in lung viral load and limited inflammatory response.

No MeSH data available.


Related in: MedlinePlus

Lung cell composition in response to influenza infection is altered by exercise treatment in obese and non-obese mice.Subsets of mice from each treatment group were infected with A/PR/8/34 then euthanized at the indicated time points post-infection. Total cell infiltration was quantified and percentages of the specific immune cell populations were characterized in bronchoalveolar lavage (BAL) fluid using flow cytometry. The percentage of each cell population is expressed as percent of gated parent population per total BAL cells. 5A) Percentage of macrophages, dendritic cells, and plasmacytoid dendritic cells (pDC’s) were detected at d1 p.i., 5B) macrophages, dendritic cells, pDC’s, neutrophils, NK cells, TNFα/iNOS producing dendritic cells (TipDC’s) and inflammatory monocytes were similarly detected at d3 p.i. 5C) At d8 p.i., the percentage of macrophages, dendritic cells, inflammatory monocytes, neutrophils, CD4+ T cells and CD8+ T cells were also determined. The acronym ‘n.d.’ indicates that the cell population was not-detectable in the non-infected group. Based on the results of a two-way ANOVA, a significant (p < 0.05) interaction between diet and exercise (d X e*) was determined (d X e+; p < 0.1); d* indicates a significant main effect of diet at p < 0.05, (d+; p < 0.10); e* indicates a significant main effect of exercise at p < 0.05 (e+; p < 0.10). Sample size (n) is 5–13 per infected group; n = 1–3 for the non-infected groups. Data shown as mean ± SEM. Results are representative of two separate experiments.
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pone.0129713.g005: Lung cell composition in response to influenza infection is altered by exercise treatment in obese and non-obese mice.Subsets of mice from each treatment group were infected with A/PR/8/34 then euthanized at the indicated time points post-infection. Total cell infiltration was quantified and percentages of the specific immune cell populations were characterized in bronchoalveolar lavage (BAL) fluid using flow cytometry. The percentage of each cell population is expressed as percent of gated parent population per total BAL cells. 5A) Percentage of macrophages, dendritic cells, and plasmacytoid dendritic cells (pDC’s) were detected at d1 p.i., 5B) macrophages, dendritic cells, pDC’s, neutrophils, NK cells, TNFα/iNOS producing dendritic cells (TipDC’s) and inflammatory monocytes were similarly detected at d3 p.i. 5C) At d8 p.i., the percentage of macrophages, dendritic cells, inflammatory monocytes, neutrophils, CD4+ T cells and CD8+ T cells were also determined. The acronym ‘n.d.’ indicates that the cell population was not-detectable in the non-infected group. Based on the results of a two-way ANOVA, a significant (p < 0.05) interaction between diet and exercise (d X e*) was determined (d X e+; p < 0.1); d* indicates a significant main effect of diet at p < 0.05, (d+; p < 0.10); e* indicates a significant main effect of exercise at p < 0.05 (e+; p < 0.10). Sample size (n) is 5–13 per infected group; n = 1–3 for the non-infected groups. Data shown as mean ± SEM. Results are representative of two separate experiments.

Mentions: BAL fluid was collected for total cell counts (Fig 4), the total number of specific cell populations (Fig 4), and the percentages of infiltrating immune cells (Fig 5). With respect to number of cells, exercise resulted in a modest increase in cell number in both obese and non-obese mice at d1 p.i. (e+; p < 0.1). The effect of exercise at later time points varied by obesity status (d*; p < 0.05); Non-ob EX mice had significantly fewer cells recruited to the lungs relative to Non-ob NO-EX, whereas Ob EX mice had a greater number of cells recruited than Ob NO-EX mice (Fig 4) (d3 p.i.; d X e+; p < 0.1 and d8 p.i.; d X e*; p < 0.05). Cell recruitment was highly correlated with lung viral load in non-obese mice (d3 p.i., Pearson correlation coefficient = 0.420, p < 0.001; at d8 p.i., Pearson correlation coefficient = 0.123, p = 0.01) and therefore, in non-obese mice the reduction in cell number resulting from exercise treatment may reflect decreased viral load (S3 Fig). However, in obese mice, the typical relationship between lung viral load and cell recruitment was not present, suggesting dysregulation in the recruitment of cells in proportion to viral load. At d3 p.i., obese mice had fewer macrophages, conventional dendritic cells (cDC), plasmacytoid dendritic cells (pDC), TNFα/iNOS producing dendritic cells (TipDC), natural killer cells (NK), inflammatory monocytes, and neutrophils compared to non-obese mice (Fig 4) (d*; p < 0.05 and d+; p < 0.1). Exercise treatment of obese mice partially restored cell recruitment for all cell types except cDC and NK cells at day 3 (e*; p < 0.05, d X e*; p < 0.05 and d X e+ p < 0.1). By d8 p.i., exercise completely restored the number of macrophages, cDC, inflammatory monocytes, neutrophils, and actually increased the number of CD8+ T cells relative to non-obese mice (d X e+; p < 0.1) (Fig 4).


Exercise Improves Host Response to Influenza Viral Infection in Obese and Non-Obese Mice through Different Mechanisms.

Warren KJ, Olson MM, Thompson NJ, Cahill ML, Wyatt TA, Yoon KJ, Loiacono CM, Kohut ML - PLoS ONE (2015)

Lung cell composition in response to influenza infection is altered by exercise treatment in obese and non-obese mice.Subsets of mice from each treatment group were infected with A/PR/8/34 then euthanized at the indicated time points post-infection. Total cell infiltration was quantified and percentages of the specific immune cell populations were characterized in bronchoalveolar lavage (BAL) fluid using flow cytometry. The percentage of each cell population is expressed as percent of gated parent population per total BAL cells. 5A) Percentage of macrophages, dendritic cells, and plasmacytoid dendritic cells (pDC’s) were detected at d1 p.i., 5B) macrophages, dendritic cells, pDC’s, neutrophils, NK cells, TNFα/iNOS producing dendritic cells (TipDC’s) and inflammatory monocytes were similarly detected at d3 p.i. 5C) At d8 p.i., the percentage of macrophages, dendritic cells, inflammatory monocytes, neutrophils, CD4+ T cells and CD8+ T cells were also determined. The acronym ‘n.d.’ indicates that the cell population was not-detectable in the non-infected group. Based on the results of a two-way ANOVA, a significant (p < 0.05) interaction between diet and exercise (d X e*) was determined (d X e+; p < 0.1); d* indicates a significant main effect of diet at p < 0.05, (d+; p < 0.10); e* indicates a significant main effect of exercise at p < 0.05 (e+; p < 0.10). Sample size (n) is 5–13 per infected group; n = 1–3 for the non-infected groups. Data shown as mean ± SEM. Results are representative of two separate experiments.
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Related In: Results  -  Collection

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pone.0129713.g005: Lung cell composition in response to influenza infection is altered by exercise treatment in obese and non-obese mice.Subsets of mice from each treatment group were infected with A/PR/8/34 then euthanized at the indicated time points post-infection. Total cell infiltration was quantified and percentages of the specific immune cell populations were characterized in bronchoalveolar lavage (BAL) fluid using flow cytometry. The percentage of each cell population is expressed as percent of gated parent population per total BAL cells. 5A) Percentage of macrophages, dendritic cells, and plasmacytoid dendritic cells (pDC’s) were detected at d1 p.i., 5B) macrophages, dendritic cells, pDC’s, neutrophils, NK cells, TNFα/iNOS producing dendritic cells (TipDC’s) and inflammatory monocytes were similarly detected at d3 p.i. 5C) At d8 p.i., the percentage of macrophages, dendritic cells, inflammatory monocytes, neutrophils, CD4+ T cells and CD8+ T cells were also determined. The acronym ‘n.d.’ indicates that the cell population was not-detectable in the non-infected group. Based on the results of a two-way ANOVA, a significant (p < 0.05) interaction between diet and exercise (d X e*) was determined (d X e+; p < 0.1); d* indicates a significant main effect of diet at p < 0.05, (d+; p < 0.10); e* indicates a significant main effect of exercise at p < 0.05 (e+; p < 0.10). Sample size (n) is 5–13 per infected group; n = 1–3 for the non-infected groups. Data shown as mean ± SEM. Results are representative of two separate experiments.
Mentions: BAL fluid was collected for total cell counts (Fig 4), the total number of specific cell populations (Fig 4), and the percentages of infiltrating immune cells (Fig 5). With respect to number of cells, exercise resulted in a modest increase in cell number in both obese and non-obese mice at d1 p.i. (e+; p < 0.1). The effect of exercise at later time points varied by obesity status (d*; p < 0.05); Non-ob EX mice had significantly fewer cells recruited to the lungs relative to Non-ob NO-EX, whereas Ob EX mice had a greater number of cells recruited than Ob NO-EX mice (Fig 4) (d3 p.i.; d X e+; p < 0.1 and d8 p.i.; d X e*; p < 0.05). Cell recruitment was highly correlated with lung viral load in non-obese mice (d3 p.i., Pearson correlation coefficient = 0.420, p < 0.001; at d8 p.i., Pearson correlation coefficient = 0.123, p = 0.01) and therefore, in non-obese mice the reduction in cell number resulting from exercise treatment may reflect decreased viral load (S3 Fig). However, in obese mice, the typical relationship between lung viral load and cell recruitment was not present, suggesting dysregulation in the recruitment of cells in proportion to viral load. At d3 p.i., obese mice had fewer macrophages, conventional dendritic cells (cDC), plasmacytoid dendritic cells (pDC), TNFα/iNOS producing dendritic cells (TipDC), natural killer cells (NK), inflammatory monocytes, and neutrophils compared to non-obese mice (Fig 4) (d*; p < 0.05 and d+; p < 0.1). Exercise treatment of obese mice partially restored cell recruitment for all cell types except cDC and NK cells at day 3 (e*; p < 0.05, d X e*; p < 0.05 and d X e+ p < 0.1). By d8 p.i., exercise completely restored the number of macrophages, cDC, inflammatory monocytes, neutrophils, and actually increased the number of CD8+ T cells relative to non-obese mice (d X e+; p < 0.1) (Fig 4).

Bottom Line: Obesity has been associated with greater severity of influenza virus infection and impaired host defense.Exercise reversed the obesity-associated delay in bronchoalveolar-lavage (BAL) cell infiltration, restored BAL cytokine and chemokine production, and increased ciliary beat frequency and IFNα-related gene expression.In contrast, in non-obese mice exercise treatment results in an early reduction in lung viral load and limited inflammatory response.

View Article: PubMed Central - PubMed

Affiliation: Immunobiology Program, Iowa State University, Ames, IA, United States of America.

ABSTRACT
Obesity has been associated with greater severity of influenza virus infection and impaired host defense. Exercise may confer health benefits even when weight loss is not achieved, but it has not been determined if regular exercise improves immune defense against influenza A virus (IAV) in the obese condition. In this study, diet-induced obese mice and lean control mice exercised for eight weeks followed by influenza viral infection. Exercise reduced disease severity in both obese and non-obese mice, but the mechanisms differed. Exercise reversed the obesity-associated delay in bronchoalveolar-lavage (BAL) cell infiltration, restored BAL cytokine and chemokine production, and increased ciliary beat frequency and IFNα-related gene expression. In non-obese mice, exercise treatment reduced lung viral load, increased Type-I-IFN-related gene expression early during infection, but reduced BAL inflammatory cytokines and chemokines. In both obese and non-obese mice, exercise increased serum anti-influenza virus specific IgG2c antibody, increased CD8+ T cell percentage in BAL, and reduced TNFα by influenza viral NP-peptide-responding CD8+ T cells. Overall, the results suggest that exercise "restores" the immune response of obese mice to a phenotype similar to non-obese mice by improving the delay in immune activation. In contrast, in non-obese mice exercise treatment results in an early reduction in lung viral load and limited inflammatory response.

No MeSH data available.


Related in: MedlinePlus