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Role of IL-17A on resolution of pulmonary C. neoformans infection.

Wozniak KL, Hardison SE, Kolls JK, Wormley FL - PLoS ONE (2011)

Bottom Line: Signaling through the IFN-γ receptor (R) was required for increased IL-17A production, however, a Th17-type cytokine profile was not observed.Neutrophils were found to be the predominant leukocytic source of IL-17A, rather than T cells, suggesting that the IL-17A produced was not part of a T cell-mediated Th17-type immune response.Also, depletion of IL-17A did not affect the local production of other cytokines.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, The University of Texas at San Antonio, San Antonio, Texas, United States of America. Karen.Wozniak@utsa.edu

ABSTRACT
The current studies evaluated the role of interleukin (IL)-17A in the induction of protective immunity against pulmonary cryptococcosis in mice. Protection against pulmonary infection with C. neoformans strain H99γ was associated with increased IL-17A production. Signaling through the IFN-γ receptor (R) was required for increased IL-17A production, however, a Th17-type cytokine profile was not observed. Neutrophils were found to be the predominant leukocytic source of IL-17A, rather than T cells, suggesting that the IL-17A produced was not part of a T cell-mediated Th17-type immune response. Depletion of IL-17A in mice during pulmonary infection with C. neoformans strain H99γ resulted in an initial increase in pulmonary fungal burden, but had no effect on cryptococcal burden at later time points. Also, depletion of IL-17A did not affect the local production of other cytokines. IL-17RA⁻/⁻ mice infected with C. neoformans strain H99γ survived the primary infection as well as a secondary challenge with wild-type cryptococci. However, dissemination of the wild-type strain to the brain was noted in the surviving IL-17RA⁻/⁻ mice. Altogether, our results suggested that IL-17A may be important for optimal protective immune responsiveness during pulmonary C. neoformans infection, but protective Th1-type immune responses are sufficient for protection against cryptococcal infection.

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IL-17A depletion does not affect resolution of cryptococcal infection.BALB/c mice were infected with C. neoformans strain H99γ, and then treated with 100 µg of anti-IL-17A neutralizing antibody or isotype control IgG2a via the intranasal route four hours following infection. Treatment was repeated every four days thereafter. The lungs from depleted mice and isotype control-treated mice were excised at days 7 and 14 post inoculation and assayed for IL-17A production (A) and cryptococcal fungal burden (B). Data are cumulative of five experiments utilizing 5 mice per group. Asterisks (*) indicate where significant decreases were observed in IL-17A depleted mice compared to isotype-control treated mice following infection with C. neoformans strain H99γ (P<0.05). Separate mice were used for each time point.
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pone-0017204-g004: IL-17A depletion does not affect resolution of cryptococcal infection.BALB/c mice were infected with C. neoformans strain H99γ, and then treated with 100 µg of anti-IL-17A neutralizing antibody or isotype control IgG2a via the intranasal route four hours following infection. Treatment was repeated every four days thereafter. The lungs from depleted mice and isotype control-treated mice were excised at days 7 and 14 post inoculation and assayed for IL-17A production (A) and cryptococcal fungal burden (B). Data are cumulative of five experiments utilizing 5 mice per group. Asterisks (*) indicate where significant decreases were observed in IL-17A depleted mice compared to isotype-control treated mice following infection with C. neoformans strain H99γ (P<0.05). Separate mice were used for each time point.

Mentions: Previous studies have suggested that IL-17A may play a role in protection against experimental pulmonary crytococcosis [14]. We therefore examined the effects of IL-17A depletion on the development of protection in mice given an experimental pulmonary infection with C. neoformans strain H99γ. Mice were treated intranasally with anti-IL-17A monoclonal antibody or isotype-control antibody beginning at 4 hours post-inoculation and continued every 4 days throughout the experiment. We observed a significant reduction in IL-17A production in lung homogenates of mice treated with the anti-IL-17A antibody at days 7 and 14 post-infection compared to mice treated with the isotype control antibody (Figure 4A). Examination of other cytokines and chemokines in lung homogenates revealed no significant differences between isotype-control and anti-IL-17A antibody treated mice (Table 1). Mice treated with anti-IL-17A antibody had significantly increased pulmonary fungal burden compared to mice treated with the isotype control antibody (P<0.002) at day 7 post-infection (Figure 4B). No differences in pulmonary fungal burden were observed at day 14 post-infection (Figure 4B). Although all leukocytes are significantly increased in infected mice compared to naïve controls, we observed no significant differences in leukocyte populations in H99γ-infected isotype control treated mice compared to IL-17A depleted mice at each time point tested (Figure 5).


Role of IL-17A on resolution of pulmonary C. neoformans infection.

Wozniak KL, Hardison SE, Kolls JK, Wormley FL - PLoS ONE (2011)

IL-17A depletion does not affect resolution of cryptococcal infection.BALB/c mice were infected with C. neoformans strain H99γ, and then treated with 100 µg of anti-IL-17A neutralizing antibody or isotype control IgG2a via the intranasal route four hours following infection. Treatment was repeated every four days thereafter. The lungs from depleted mice and isotype control-treated mice were excised at days 7 and 14 post inoculation and assayed for IL-17A production (A) and cryptococcal fungal burden (B). Data are cumulative of five experiments utilizing 5 mice per group. Asterisks (*) indicate where significant decreases were observed in IL-17A depleted mice compared to isotype-control treated mice following infection with C. neoformans strain H99γ (P<0.05). Separate mice were used for each time point.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3040760&req=5

pone-0017204-g004: IL-17A depletion does not affect resolution of cryptococcal infection.BALB/c mice were infected with C. neoformans strain H99γ, and then treated with 100 µg of anti-IL-17A neutralizing antibody or isotype control IgG2a via the intranasal route four hours following infection. Treatment was repeated every four days thereafter. The lungs from depleted mice and isotype control-treated mice were excised at days 7 and 14 post inoculation and assayed for IL-17A production (A) and cryptococcal fungal burden (B). Data are cumulative of five experiments utilizing 5 mice per group. Asterisks (*) indicate where significant decreases were observed in IL-17A depleted mice compared to isotype-control treated mice following infection with C. neoformans strain H99γ (P<0.05). Separate mice were used for each time point.
Mentions: Previous studies have suggested that IL-17A may play a role in protection against experimental pulmonary crytococcosis [14]. We therefore examined the effects of IL-17A depletion on the development of protection in mice given an experimental pulmonary infection with C. neoformans strain H99γ. Mice were treated intranasally with anti-IL-17A monoclonal antibody or isotype-control antibody beginning at 4 hours post-inoculation and continued every 4 days throughout the experiment. We observed a significant reduction in IL-17A production in lung homogenates of mice treated with the anti-IL-17A antibody at days 7 and 14 post-infection compared to mice treated with the isotype control antibody (Figure 4A). Examination of other cytokines and chemokines in lung homogenates revealed no significant differences between isotype-control and anti-IL-17A antibody treated mice (Table 1). Mice treated with anti-IL-17A antibody had significantly increased pulmonary fungal burden compared to mice treated with the isotype control antibody (P<0.002) at day 7 post-infection (Figure 4B). No differences in pulmonary fungal burden were observed at day 14 post-infection (Figure 4B). Although all leukocytes are significantly increased in infected mice compared to naïve controls, we observed no significant differences in leukocyte populations in H99γ-infected isotype control treated mice compared to IL-17A depleted mice at each time point tested (Figure 5).

Bottom Line: Signaling through the IFN-γ receptor (R) was required for increased IL-17A production, however, a Th17-type cytokine profile was not observed.Neutrophils were found to be the predominant leukocytic source of IL-17A, rather than T cells, suggesting that the IL-17A produced was not part of a T cell-mediated Th17-type immune response.Also, depletion of IL-17A did not affect the local production of other cytokines.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, The University of Texas at San Antonio, San Antonio, Texas, United States of America. Karen.Wozniak@utsa.edu

ABSTRACT
The current studies evaluated the role of interleukin (IL)-17A in the induction of protective immunity against pulmonary cryptococcosis in mice. Protection against pulmonary infection with C. neoformans strain H99γ was associated with increased IL-17A production. Signaling through the IFN-γ receptor (R) was required for increased IL-17A production, however, a Th17-type cytokine profile was not observed. Neutrophils were found to be the predominant leukocytic source of IL-17A, rather than T cells, suggesting that the IL-17A produced was not part of a T cell-mediated Th17-type immune response. Depletion of IL-17A in mice during pulmonary infection with C. neoformans strain H99γ resulted in an initial increase in pulmonary fungal burden, but had no effect on cryptococcal burden at later time points. Also, depletion of IL-17A did not affect the local production of other cytokines. IL-17RA⁻/⁻ mice infected with C. neoformans strain H99γ survived the primary infection as well as a secondary challenge with wild-type cryptococci. However, dissemination of the wild-type strain to the brain was noted in the surviving IL-17RA⁻/⁻ mice. Altogether, our results suggested that IL-17A may be important for optimal protective immune responsiveness during pulmonary C. neoformans infection, but protective Th1-type immune responses are sufficient for protection against cryptococcal infection.

Show MeSH
Related in: MedlinePlus