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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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Pulmonary infection with C. neoformans strain H99γ results in significant IL-17A, but not Th17, cytokine production in the lungs.BALB/c mice were given an intranasal inoculation with C. neoformans strain H99 or H99γ. Lung homogenates were prepared from lungs excised on day 7 post-inoculation and assayed for IL-6, IL-17A, IL-21, IL-23, and TGF-β cytokine production. Data are cumulative of four experiments utilizing 5 mice each per group. Asterisks (*) indicate where significant differences were observed (P<0.0001).
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pone-0017204-g001: Pulmonary infection with C. neoformans strain H99γ results in significant IL-17A, but not Th17, cytokine production in the lungs.BALB/c mice were given an intranasal inoculation with C. neoformans strain H99 or H99γ. Lung homogenates were prepared from lungs excised on day 7 post-inoculation and assayed for IL-6, IL-17A, IL-21, IL-23, and TGF-β cytokine production. Data are cumulative of four experiments utilizing 5 mice each per group. Asterisks (*) indicate where significant differences were observed (P<0.0001).

Mentions: Previous studies in our laboratory have shown that infection with an IFN-γ-producing C. neoformans strain, H99γ, results in a significant increase in pulmonary IL-17A cytokine production on day 7 post-inoculation compared to mice infected with the parental C. neoformans strain H99 [14], [16]. However, it remains unclear whether the increase in IL-17A production observed in the lungs of mice infected with C. neoformans strain H99γ is coupled to an overall Th17-type cytokine response. We therefore determined the expression of cytokines associated with the induction of Th17-cytokine responses (IL-6, IL-17A, IL-21, IL-23, and TGF-β) in total lung homogenates derived from mice infected with wild-type C. neoformans strain H99 or the transgenic C. neoformans strain H99γ on day 7 post-inoculation. We observed a significant increase in IL-6 and IL-17 (Figure 1) in lung homogenates derived from C. neoformans strain H99γ infected mice compared to those obtained from mice infected with wild-type yeast (P<0.0001 for IL-6 and IL-17A) as previously described [14]. However, no significant differences in the production of IL-21, IL-23, or TGF-β were observed in the lungs of mice infected with wild-type C. neoformans strain H99 compared to mice infected with the transgenic C. neoformans strain H99γ. Thus, the significant increase in IL-17A production observed in the lungs of mice during infection with the transgenic C. neoformans strain H99γ appears not to be associated with a general induction of Th17-type cytokines.


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

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

Pulmonary infection with C. neoformans strain H99γ results in significant IL-17A, but not Th17, cytokine production in the lungs.BALB/c mice were given an intranasal inoculation with C. neoformans strain H99 or H99γ. Lung homogenates were prepared from lungs excised on day 7 post-inoculation and assayed for IL-6, IL-17A, IL-21, IL-23, and TGF-β cytokine production. Data are cumulative of four experiments utilizing 5 mice each per group. Asterisks (*) indicate where significant differences were observed (P<0.0001).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3040760&req=5

pone-0017204-g001: Pulmonary infection with C. neoformans strain H99γ results in significant IL-17A, but not Th17, cytokine production in the lungs.BALB/c mice were given an intranasal inoculation with C. neoformans strain H99 or H99γ. Lung homogenates were prepared from lungs excised on day 7 post-inoculation and assayed for IL-6, IL-17A, IL-21, IL-23, and TGF-β cytokine production. Data are cumulative of four experiments utilizing 5 mice each per group. Asterisks (*) indicate where significant differences were observed (P<0.0001).
Mentions: Previous studies in our laboratory have shown that infection with an IFN-γ-producing C. neoformans strain, H99γ, results in a significant increase in pulmonary IL-17A cytokine production on day 7 post-inoculation compared to mice infected with the parental C. neoformans strain H99 [14], [16]. However, it remains unclear whether the increase in IL-17A production observed in the lungs of mice infected with C. neoformans strain H99γ is coupled to an overall Th17-type cytokine response. We therefore determined the expression of cytokines associated with the induction of Th17-cytokine responses (IL-6, IL-17A, IL-21, IL-23, and TGF-β) in total lung homogenates derived from mice infected with wild-type C. neoformans strain H99 or the transgenic C. neoformans strain H99γ on day 7 post-inoculation. We observed a significant increase in IL-6 and IL-17 (Figure 1) in lung homogenates derived from C. neoformans strain H99γ infected mice compared to those obtained from mice infected with wild-type yeast (P<0.0001 for IL-6 and IL-17A) as previously described [14]. However, no significant differences in the production of IL-21, IL-23, or TGF-β were observed in the lungs of mice infected with wild-type C. neoformans strain H99 compared to mice infected with the transgenic C. neoformans strain H99γ. Thus, the significant increase in IL-17A production observed in the lungs of mice during infection with the transgenic C. neoformans strain H99γ appears not to be associated with a general induction of Th17-type cytokines.

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