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Allergic lung inflammation alters neither susceptibility to Streptococcus pneumoniae infection nor inducibility of innate resistance in mice.

Clement CG, Tuvim MJ, Evans CM, Tuvin DM, Dickey BF, Evans SE - Respir. Res. (2009)

Bottom Line: Allergic inflammation was associated with predominantly eosinophilic infiltration, whereas the lysate-induced response was primarily neutrophilic.The presence of allergic inflammation did not significantly alter the neutrophilic response to the lysate, and did not affect the induced bacterial killing within the lungs.These results suggest that allergic airway inflammation neither promotes nor inhibits progression of pneumococcal lung infection in mice, nor does it influence the successful induction of stimulated innate resistance to bacteria.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pulmonary Medicine, The University of Texas M, D, Anderson Cancer Center, Houston, TX 77030, USA. cgmoron@utmb.edu

ABSTRACT

Background: Protective host responses to respiratory pathogens are typically characterized by inflammation. However, lung inflammation is not always protective and it may even become deleterious to the host. We have recently reported substantial protection against Streptococcus pneumoniae (pneumococcal) pneumonia by induction of a robust inflammatory innate immune response to an inhaled bacterial lysate. Conversely, the allergic inflammation associated with asthma has been proposed to promote susceptibility to pneumococcal disease. This study sought to determine whether preexisting allergic lung inflammation influences the progression of pneumococcal pneumonia or reduces the inducibilty of protective innate immunity against bacteria.

Methods: To compare the effect of different inflammatory and secretory stimuli on defense against pneumonia, intraperitoneally ovalbumin-sensitized mice were challenged with inhaled pneumococci following exposure to various inhaled combinations of ovalbumin, ATP, and/or a bacterial lysate. Thus, allergic inflammation, mucin degranulation and/or stimulated innate resistance were induced prior to the infectious challenge. Pathogen killing was evaluated by assessing bacterial CFUs of lung homogenates immediately after infection, the inflammatory response to the different conditions was evaluated by measurement of cell counts of bronchoalveolar lavage fluid 18 hours after challenge, and mouse survival was assessed after seven days.

Results: We found no differences in survival of mice with and without allergic inflammation, nor did the induction of mucin degranulation alter survival. As we have found previously, mice treated with the bacterial lysate demonstrated substantially increased survival at seven days, and this was not altered by the presence of allergic inflammation or mucin degranulation. Allergic inflammation was associated with predominantly eosinophilic infiltration, whereas the lysate-induced response was primarily neutrophilic. The presence of allergic inflammation did not significantly alter the neutrophilic response to the lysate, and did not affect the induced bacterial killing within the lungs.

Conclusion: These results suggest that allergic airway inflammation neither promotes nor inhibits progression of pneumococcal lung infection in mice, nor does it influence the successful induction of stimulated innate resistance to bacteria.

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Leukocyte infiltration following various inflammatory stimuli. Differential cell counts were performed on bronchoalveolar lavage fluid from mice following treatment with different combinations of inflammatory stimuli without (upper panel) or with (lower panel) infection with S. pneumoniae (3.2 × 1010 CFU/ml) 18 h earlier. The experiments were performed simultaneously with identical treatments, except for the infectious challenge. (3 mice/group, mean ± SEM).
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Figure 4: Leukocyte infiltration following various inflammatory stimuli. Differential cell counts were performed on bronchoalveolar lavage fluid from mice following treatment with different combinations of inflammatory stimuli without (upper panel) or with (lower panel) infection with S. pneumoniae (3.2 × 1010 CFU/ml) 18 h earlier. The experiments were performed simultaneously with identical treatments, except for the infectious challenge. (3 mice/group, mean ± SEM).

Mentions: In order to better characterize the lungs' responses to various inflammatory stimuli, we characterized the cellular influx of the airway lining fluid collected by BAL. As shown in Figure 4, the allergic and bacteria-protective stimuli induced influx of distinctly different cell populations. Exposure of sensitized mice to inhaled ovalbumin induced modest increases in macrophages and eosinophils, whereas treatment with NTHi lysate primarily induced infiltration with neutrophils. These patterns persisted when both treatments were applied to the same animal. For example, eosinophils increased following OVA challenge (0 detected eosinophils at baseline vs. 0.65 × 105 eosinophils after challenge, p = 0.047), whereas there was no difference detected when OVA challenged mice were compared to those challenged with OVA then treated with NTHi lysate (0.77 × 105 eosinophils, p = 0.64). Similarly, the brisk induction of neutrophils after NTHi lysate treatment (0.15 × 105 PMNs at baseline vs. 9.52 × 105 PMNs after treatment, p < 0.0001) was not significantly altered by the presence of allergic inflammation (8.20 × 105 PMNs, p = 0.29).


Allergic lung inflammation alters neither susceptibility to Streptococcus pneumoniae infection nor inducibility of innate resistance in mice.

Clement CG, Tuvim MJ, Evans CM, Tuvin DM, Dickey BF, Evans SE - Respir. Res. (2009)

Leukocyte infiltration following various inflammatory stimuli. Differential cell counts were performed on bronchoalveolar lavage fluid from mice following treatment with different combinations of inflammatory stimuli without (upper panel) or with (lower panel) infection with S. pneumoniae (3.2 × 1010 CFU/ml) 18 h earlier. The experiments were performed simultaneously with identical treatments, except for the infectious challenge. (3 mice/group, mean ± SEM).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2724420&req=5

Figure 4: Leukocyte infiltration following various inflammatory stimuli. Differential cell counts were performed on bronchoalveolar lavage fluid from mice following treatment with different combinations of inflammatory stimuli without (upper panel) or with (lower panel) infection with S. pneumoniae (3.2 × 1010 CFU/ml) 18 h earlier. The experiments were performed simultaneously with identical treatments, except for the infectious challenge. (3 mice/group, mean ± SEM).
Mentions: In order to better characterize the lungs' responses to various inflammatory stimuli, we characterized the cellular influx of the airway lining fluid collected by BAL. As shown in Figure 4, the allergic and bacteria-protective stimuli induced influx of distinctly different cell populations. Exposure of sensitized mice to inhaled ovalbumin induced modest increases in macrophages and eosinophils, whereas treatment with NTHi lysate primarily induced infiltration with neutrophils. These patterns persisted when both treatments were applied to the same animal. For example, eosinophils increased following OVA challenge (0 detected eosinophils at baseline vs. 0.65 × 105 eosinophils after challenge, p = 0.047), whereas there was no difference detected when OVA challenged mice were compared to those challenged with OVA then treated with NTHi lysate (0.77 × 105 eosinophils, p = 0.64). Similarly, the brisk induction of neutrophils after NTHi lysate treatment (0.15 × 105 PMNs at baseline vs. 9.52 × 105 PMNs after treatment, p < 0.0001) was not significantly altered by the presence of allergic inflammation (8.20 × 105 PMNs, p = 0.29).

Bottom Line: Allergic inflammation was associated with predominantly eosinophilic infiltration, whereas the lysate-induced response was primarily neutrophilic.The presence of allergic inflammation did not significantly alter the neutrophilic response to the lysate, and did not affect the induced bacterial killing within the lungs.These results suggest that allergic airway inflammation neither promotes nor inhibits progression of pneumococcal lung infection in mice, nor does it influence the successful induction of stimulated innate resistance to bacteria.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pulmonary Medicine, The University of Texas M, D, Anderson Cancer Center, Houston, TX 77030, USA. cgmoron@utmb.edu

ABSTRACT

Background: Protective host responses to respiratory pathogens are typically characterized by inflammation. However, lung inflammation is not always protective and it may even become deleterious to the host. We have recently reported substantial protection against Streptococcus pneumoniae (pneumococcal) pneumonia by induction of a robust inflammatory innate immune response to an inhaled bacterial lysate. Conversely, the allergic inflammation associated with asthma has been proposed to promote susceptibility to pneumococcal disease. This study sought to determine whether preexisting allergic lung inflammation influences the progression of pneumococcal pneumonia or reduces the inducibilty of protective innate immunity against bacteria.

Methods: To compare the effect of different inflammatory and secretory stimuli on defense against pneumonia, intraperitoneally ovalbumin-sensitized mice were challenged with inhaled pneumococci following exposure to various inhaled combinations of ovalbumin, ATP, and/or a bacterial lysate. Thus, allergic inflammation, mucin degranulation and/or stimulated innate resistance were induced prior to the infectious challenge. Pathogen killing was evaluated by assessing bacterial CFUs of lung homogenates immediately after infection, the inflammatory response to the different conditions was evaluated by measurement of cell counts of bronchoalveolar lavage fluid 18 hours after challenge, and mouse survival was assessed after seven days.

Results: We found no differences in survival of mice with and without allergic inflammation, nor did the induction of mucin degranulation alter survival. As we have found previously, mice treated with the bacterial lysate demonstrated substantially increased survival at seven days, and this was not altered by the presence of allergic inflammation or mucin degranulation. Allergic inflammation was associated with predominantly eosinophilic infiltration, whereas the lysate-induced response was primarily neutrophilic. The presence of allergic inflammation did not significantly alter the neutrophilic response to the lysate, and did not affect the induced bacterial killing within the lungs.

Conclusion: These results suggest that allergic airway inflammation neither promotes nor inhibits progression of pneumococcal lung infection in mice, nor does it influence the successful induction of stimulated innate resistance to bacteria.

Show MeSH
Related in: MedlinePlus