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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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Induction of IL-17A production during C. neoformans strain H99γ infection requires IFN-γR expression.BALB/c and IFN-γR−/− mice were given an intranasal inoculation with either C. neoformans strain H99 or H99γ. Naïve mice were used as controls for pulmonary cytokines. Lungs were excised at day 7 post-inoculation, and pulmonary cryptococcal burden (A) and cytokine production (B) quantified. Fungal burden results are expressed as mean log CFU per milliliter ± standard errors of the means. A. Asterisks (*) indicate where significant decreases in CFU were observed in IFN-γR −/− mice compared to wild-type BALB/c mice (P<0.01). B. Asterisks (*) indicate where significant differences in cytokines were observed (P<0.02). Data are cumulative of two experiments using 5 mice per group.
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pone-0017204-g003: Induction of IL-17A production during C. neoformans strain H99γ infection requires IFN-γR expression.BALB/c and IFN-γR−/− mice were given an intranasal inoculation with either C. neoformans strain H99 or H99γ. Naïve mice were used as controls for pulmonary cytokines. Lungs were excised at day 7 post-inoculation, and pulmonary cryptococcal burden (A) and cytokine production (B) quantified. Fungal burden results are expressed as mean log CFU per milliliter ± standard errors of the means. A. Asterisks (*) indicate where significant decreases in CFU were observed in IFN-γR −/− mice compared to wild-type BALB/c mice (P<0.01). B. Asterisks (*) indicate where significant differences in cytokines were observed (P<0.02). Data are cumulative of two experiments using 5 mice per group.

Mentions: Our studies suggest that signaling through the IFN-γR may be necessary for the increase in IL-17A production observed in the lungs of mice inoculated with C. neoformans strain H99γ. To evaluate this hypothesis, IFN-γR−/− and wild-type (WT) BALB/c mice were inoculated with C. neoformans strain H99γ or C. neoformans strain H99 and thereafter examined for pulmonary fungal burden, cytokine production, and leukocyte infiltration at day 7 post-infection. Results showed that IFN-γR−/− mice had significantly increased pulmonary fungal burden compared to WT mice when infected with C. neoformans strain H99γ, but no change in fungal burden was detected between IFN-γR−/− mice and WT mice during infection with the wild-type strain, C. neoformans strain H99 (Figure 3A). Furthermore, cytokine analysis showed that the IFN-γR−/− mice had significantly reduced levels of pro-inflammatory (IL-1α, IL-1β, and IL-6), IL-12p40, IL-17, and chemokine (G-CSF and CXCL1) production compared to WT mice during infection with C. neoformans strain H99γ (Figure 3B). No differences were observed in cytokine production in KO vs WT mice infected with C. neoformans strain H99.


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

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

Induction of IL-17A production during C. neoformans strain H99γ infection requires IFN-γR expression.BALB/c and IFN-γR−/− mice were given an intranasal inoculation with either C. neoformans strain H99 or H99γ. Naïve mice were used as controls for pulmonary cytokines. Lungs were excised at day 7 post-inoculation, and pulmonary cryptococcal burden (A) and cytokine production (B) quantified. Fungal burden results are expressed as mean log CFU per milliliter ± standard errors of the means. A. Asterisks (*) indicate where significant decreases in CFU were observed in IFN-γR −/− mice compared to wild-type BALB/c mice (P<0.01). B. Asterisks (*) indicate where significant differences in cytokines were observed (P<0.02). Data are cumulative of two experiments using 5 mice per group.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3040760&req=5

pone-0017204-g003: Induction of IL-17A production during C. neoformans strain H99γ infection requires IFN-γR expression.BALB/c and IFN-γR−/− mice were given an intranasal inoculation with either C. neoformans strain H99 or H99γ. Naïve mice were used as controls for pulmonary cytokines. Lungs were excised at day 7 post-inoculation, and pulmonary cryptococcal burden (A) and cytokine production (B) quantified. Fungal burden results are expressed as mean log CFU per milliliter ± standard errors of the means. A. Asterisks (*) indicate where significant decreases in CFU were observed in IFN-γR −/− mice compared to wild-type BALB/c mice (P<0.01). B. Asterisks (*) indicate where significant differences in cytokines were observed (P<0.02). Data are cumulative of two experiments using 5 mice per group.
Mentions: Our studies suggest that signaling through the IFN-γR may be necessary for the increase in IL-17A production observed in the lungs of mice inoculated with C. neoformans strain H99γ. To evaluate this hypothesis, IFN-γR−/− and wild-type (WT) BALB/c mice were inoculated with C. neoformans strain H99γ or C. neoformans strain H99 and thereafter examined for pulmonary fungal burden, cytokine production, and leukocyte infiltration at day 7 post-infection. Results showed that IFN-γR−/− mice had significantly increased pulmonary fungal burden compared to WT mice when infected with C. neoformans strain H99γ, but no change in fungal burden was detected between IFN-γR−/− mice and WT mice during infection with the wild-type strain, C. neoformans strain H99 (Figure 3A). Furthermore, cytokine analysis showed that the IFN-γR−/− mice had significantly reduced levels of pro-inflammatory (IL-1α, IL-1β, and IL-6), IL-12p40, IL-17, and chemokine (G-CSF and CXCL1) production compared to WT mice during infection with C. neoformans strain H99γ (Figure 3B). No differences were observed in cytokine production in KO vs WT mice infected with C. neoformans strain H99.

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