Limits...
Early-Life Exposure to Clostridium leptum Causes Pulmonary Immunosuppression.

Huang F, Qiao HM, Yin JN, Gao Y, Ju YH, Li YN - PLoS ONE (2015)

Bottom Line: Low Clostridium leptum levels are a risk factor for the development of asthma.Early-life C. leptum exposure induced an immunosuppressive environment in the lung concurrent with increased Treg cells, resulting in the inhibition of Th1, Th2, Th9, and Th17 cell responses.These findings demonstrate a mechanism whereby C. leptum exposure modulates adaptive immunity and leads to failure to develop asthma upon OVA sensitization later in life.

View Article: PubMed Central - PubMed

Affiliation: Department of Orthopedics, China-Japan Union Hospital of Jilin University, Changchun, Jilin, PR China.

ABSTRACT

Introduction: Low Clostridium leptum levels are a risk factor for the development of asthma. C. leptum deficiency exacerbates asthma; however, the impact of early-life C. leptum exposure on cesarean-delivered mice remains unclear. This study is to determine the effects of early-life C. leptum exposure on asthma development in infant mice.

Methods: We exposed infant mice to C. leptum (fed-CL) and then induced asthma using the allergen ovalbumin (OVA).

Results: Fed-CL increased regulatory T (Treg) cells in cesarean-delivered mice compared with vaginally delivered mice. Compared with OVA-exposed mice, mice exposed to C. leptum + OVA did not develop the typical asthma phenotype, which includes airway hyper-responsiveness, cell infiltration, and T helper cell subset (Th1, Th2, Th9, Th17) inflammation. Early-life C. leptum exposure induced an immunosuppressive environment in the lung concurrent with increased Treg cells, resulting in the inhibition of Th1, Th2, Th9, and Th17 cell responses.

Conclusion: These findings demonstrate a mechanism whereby C. leptum exposure modulates adaptive immunity and leads to failure to develop asthma upon OVA sensitization later in life.

Show MeSH

Related in: MedlinePlus

Early-life fed-CL reduced airway responsiveness, BALF cell numbers, and inflammatory cell infiltration in CD asthma mice.(A) AHR determined by airway resistance in response to inhaled methacholine (MeCh). (B) Total cell numbers and differential eosinophil (Eos), neutrophil (Neutro), lymphocyte (Lymph), and macrophage (Mac) counts in BALF. Lung tissue sections were stained with hematoxylin–eosin to evaluate allergic inflammation. (C) Representative images of lung tissue sections (original magnification, ×400). (D) Scoring of the extent of inflammation via quantitative analysis of inflammatory cell infiltration in lung sections. Data are plotted as the means ± SD. ▲p < 0.05 vs. C/-/-; ★p < 0.05 vs. C/CL/-; &p < 0.05 vs. C/-/OVA.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4643994&req=5

pone.0141717.g003: Early-life fed-CL reduced airway responsiveness, BALF cell numbers, and inflammatory cell infiltration in CD asthma mice.(A) AHR determined by airway resistance in response to inhaled methacholine (MeCh). (B) Total cell numbers and differential eosinophil (Eos), neutrophil (Neutro), lymphocyte (Lymph), and macrophage (Mac) counts in BALF. Lung tissue sections were stained with hematoxylin–eosin to evaluate allergic inflammation. (C) Representative images of lung tissue sections (original magnification, ×400). (D) Scoring of the extent of inflammation via quantitative analysis of inflammatory cell infiltration in lung sections. Data are plotted as the means ± SD. ▲p < 0.05 vs. C/-/-; ★p < 0.05 vs. C/CL/-; &p < 0.05 vs. C/-/OVA.

Mentions: To investigate the effect of fed-CL in asthmatic infant mice, we fed 8-day-old CD mouse pups with C. leptum and established an asthma model after they had been weaned (Fig 2), and analyzed the pulmonary function 48 h after the final OVA challenge day. Resistance to increasing concentrations of methacholine gradually increased in the C/-/OVA and C/CL/OVA groups; resistance in both groups was significantly higher than that in the C/-/- group (Fig 3A). In contrast, resistance of the C/CL/- group was similar to that of the C/-/- group; resistance of the C/CL/OVA group was significantly reduced as compared to the C/-/OVA group (Fig 3A). Hence, oral feeding with C. leptum attenuates allergic airway resistance in asthmatic mice. Following the lung function tests, we collected and analyzed the BALF for cellularity. Total cell number, eosinophils, neutrophils, lymphocytes, and macrophages were significantly increased in the C/-/OVA mice (Fig 3B). In the C/CL/OVA group, the same cells were all noticeably decreased as compared with that in the C/-/OVA group, and their numbers were higher than that in the C/-/- and C/CL/- groups (Fig 3B). We further examined the effect of oral administration of C. leptum on allergic lung inflammation in mice, examining lung tissue sections from individual mice under hematoxylin–eosin staining. We observed airway epithelial hyperemia and edema, many pulmonary goblet cells, and inflammatory infiltrates in the lungs of the C/-/OVA mice, but not in the C/-/- and C/CL/- mice (Fig 3C and 3D). There was an obviously lower degree of airway epithelial hyperemia and edema, fewer pulmonary goblet cells, and inflammatory infiltrates in the lungs of the C/CL/OVA mice (Fig 3C and 3D).


Early-Life Exposure to Clostridium leptum Causes Pulmonary Immunosuppression.

Huang F, Qiao HM, Yin JN, Gao Y, Ju YH, Li YN - PLoS ONE (2015)

Early-life fed-CL reduced airway responsiveness, BALF cell numbers, and inflammatory cell infiltration in CD asthma mice.(A) AHR determined by airway resistance in response to inhaled methacholine (MeCh). (B) Total cell numbers and differential eosinophil (Eos), neutrophil (Neutro), lymphocyte (Lymph), and macrophage (Mac) counts in BALF. Lung tissue sections were stained with hematoxylin–eosin to evaluate allergic inflammation. (C) Representative images of lung tissue sections (original magnification, ×400). (D) Scoring of the extent of inflammation via quantitative analysis of inflammatory cell infiltration in lung sections. Data are plotted as the means ± SD. ▲p < 0.05 vs. C/-/-; ★p < 0.05 vs. C/CL/-; &p < 0.05 vs. C/-/OVA.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4643994&req=5

pone.0141717.g003: Early-life fed-CL reduced airway responsiveness, BALF cell numbers, and inflammatory cell infiltration in CD asthma mice.(A) AHR determined by airway resistance in response to inhaled methacholine (MeCh). (B) Total cell numbers and differential eosinophil (Eos), neutrophil (Neutro), lymphocyte (Lymph), and macrophage (Mac) counts in BALF. Lung tissue sections were stained with hematoxylin–eosin to evaluate allergic inflammation. (C) Representative images of lung tissue sections (original magnification, ×400). (D) Scoring of the extent of inflammation via quantitative analysis of inflammatory cell infiltration in lung sections. Data are plotted as the means ± SD. ▲p < 0.05 vs. C/-/-; ★p < 0.05 vs. C/CL/-; &p < 0.05 vs. C/-/OVA.
Mentions: To investigate the effect of fed-CL in asthmatic infant mice, we fed 8-day-old CD mouse pups with C. leptum and established an asthma model after they had been weaned (Fig 2), and analyzed the pulmonary function 48 h after the final OVA challenge day. Resistance to increasing concentrations of methacholine gradually increased in the C/-/OVA and C/CL/OVA groups; resistance in both groups was significantly higher than that in the C/-/- group (Fig 3A). In contrast, resistance of the C/CL/- group was similar to that of the C/-/- group; resistance of the C/CL/OVA group was significantly reduced as compared to the C/-/OVA group (Fig 3A). Hence, oral feeding with C. leptum attenuates allergic airway resistance in asthmatic mice. Following the lung function tests, we collected and analyzed the BALF for cellularity. Total cell number, eosinophils, neutrophils, lymphocytes, and macrophages were significantly increased in the C/-/OVA mice (Fig 3B). In the C/CL/OVA group, the same cells were all noticeably decreased as compared with that in the C/-/OVA group, and their numbers were higher than that in the C/-/- and C/CL/- groups (Fig 3B). We further examined the effect of oral administration of C. leptum on allergic lung inflammation in mice, examining lung tissue sections from individual mice under hematoxylin–eosin staining. We observed airway epithelial hyperemia and edema, many pulmonary goblet cells, and inflammatory infiltrates in the lungs of the C/-/OVA mice, but not in the C/-/- and C/CL/- mice (Fig 3C and 3D). There was an obviously lower degree of airway epithelial hyperemia and edema, fewer pulmonary goblet cells, and inflammatory infiltrates in the lungs of the C/CL/OVA mice (Fig 3C and 3D).

Bottom Line: Low Clostridium leptum levels are a risk factor for the development of asthma.Early-life C. leptum exposure induced an immunosuppressive environment in the lung concurrent with increased Treg cells, resulting in the inhibition of Th1, Th2, Th9, and Th17 cell responses.These findings demonstrate a mechanism whereby C. leptum exposure modulates adaptive immunity and leads to failure to develop asthma upon OVA sensitization later in life.

View Article: PubMed Central - PubMed

Affiliation: Department of Orthopedics, China-Japan Union Hospital of Jilin University, Changchun, Jilin, PR China.

ABSTRACT

Introduction: Low Clostridium leptum levels are a risk factor for the development of asthma. C. leptum deficiency exacerbates asthma; however, the impact of early-life C. leptum exposure on cesarean-delivered mice remains unclear. This study is to determine the effects of early-life C. leptum exposure on asthma development in infant mice.

Methods: We exposed infant mice to C. leptum (fed-CL) and then induced asthma using the allergen ovalbumin (OVA).

Results: Fed-CL increased regulatory T (Treg) cells in cesarean-delivered mice compared with vaginally delivered mice. Compared with OVA-exposed mice, mice exposed to C. leptum + OVA did not develop the typical asthma phenotype, which includes airway hyper-responsiveness, cell infiltration, and T helper cell subset (Th1, Th2, Th9, Th17) inflammation. Early-life C. leptum exposure induced an immunosuppressive environment in the lung concurrent with increased Treg cells, resulting in the inhibition of Th1, Th2, Th9, and Th17 cell responses.

Conclusion: These findings demonstrate a mechanism whereby C. leptum exposure modulates adaptive immunity and leads to failure to develop asthma upon OVA sensitization later in life.

Show MeSH
Related in: MedlinePlus