Limits...
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.

Show MeSH

Related in: MedlinePlus

Lack of IL-17R signaling does not significantly affect resolution of infection or survival to cryptococcal infection.BALB/c mice or IL-17RA−/− mice received an intranasal inoculum of C. neoformans strain H99γ. Mice were assayed for survival through 35 days of primary infection with C. neoformans strain H99γ (A). Surviving mice were then challenged with C. neoformans strain H99 and assayed for survival through 28 days of secondary challenge (B). Culture of lung, spleen, and brain tissues at day 28 post-secondary challenge were determined from mice with positive cultures (C) and numbers of mice with positive cultures are shown above each bar. Survival data show one experiment containing nine WT and eight IL-17RA−/− mice. Asterisks (*) indicate where significant differences in fungal burden were observed in IL-17RA−/− mice compared to WT mice following infection with C. neoformans strain H99 (P<0.0001).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3040760&req=5

pone-0017204-g006: Lack of IL-17R signaling does not significantly affect resolution of infection or survival to cryptococcal infection.BALB/c mice or IL-17RA−/− mice received an intranasal inoculum of C. neoformans strain H99γ. Mice were assayed for survival through 35 days of primary infection with C. neoformans strain H99γ (A). Surviving mice were then challenged with C. neoformans strain H99 and assayed for survival through 28 days of secondary challenge (B). Culture of lung, spleen, and brain tissues at day 28 post-secondary challenge were determined from mice with positive cultures (C) and numbers of mice with positive cultures are shown above each bar. Survival data show one experiment containing nine WT and eight IL-17RA−/− mice. Asterisks (*) indicate where significant differences in fungal burden were observed in IL-17RA−/− mice compared to WT mice following infection with C. neoformans strain H99 (P<0.0001).

Mentions: Although antibody depletion significantly reduced the amount of IL-17A in lung homogenates, the depletion was not absolute. Therefore, we evaluated survival of IL-17 receptor A knock-out (IL-17RA−/−) mice given a pulmonary infection with C. neoformans strain H99γ. IL-17RA−/− mice still have the ability to produce IL-17A, but signaling through its receptor, IL-17RA, is abrogated [47]. Figure 6A demonstrates 100% survival of WT and IL-17RA−/− mice given a primary pulmonary infection with C. neoformans strain H99γ through day 35 post-inoculation. All surviving WT and IL-17RA−/−mice were subsequently re-challenged with the non-IFN-γ producing wild-type C. neoformans strain H99 on day 35 post-primary inoculation and also demonstrated 100% survival through day 28 post-secondary challenge (Figure 5B). Culture of tissue homogenates derived from re-challenged WT and IL-17RA−/− mice at day 28 post-secondary inoculation indicated no significant difference in fungal burden in lung or brain tissues (Figure 6C). Evidence of dissemination to the spleen was not observed in any surviving wild-type mice, but was observed in one surviving knock-out mouse. Interestingly, following differential plating on YPD media with and without nourseothricin (a selectable marker for the H99γ strain), colonization of spleen and brain was due to the challenge organism, strain H99, while the colonization of the lungs was due to the immunizing organism, strain H99γ. Our results suggest that IL-17A contributes to, but is not required for, the resolution of acute infection with C. neoformans strain H99γ. However, IL-17RA signaling may be needed to prevent dissemination of cryptococci from the lung to the CNS of immunized mice following re-challenge with WT cryptococci.


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

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

Lack of IL-17R signaling does not significantly affect resolution of infection or survival to cryptococcal infection.BALB/c mice or IL-17RA−/− mice received an intranasal inoculum of C. neoformans strain H99γ. Mice were assayed for survival through 35 days of primary infection with C. neoformans strain H99γ (A). Surviving mice were then challenged with C. neoformans strain H99 and assayed for survival through 28 days of secondary challenge (B). Culture of lung, spleen, and brain tissues at day 28 post-secondary challenge were determined from mice with positive cultures (C) and numbers of mice with positive cultures are shown above each bar. Survival data show one experiment containing nine WT and eight IL-17RA−/− mice. Asterisks (*) indicate where significant differences in fungal burden were observed in IL-17RA−/− mice compared to WT mice following infection with C. neoformans strain H99 (P<0.0001).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3040760&req=5

pone-0017204-g006: Lack of IL-17R signaling does not significantly affect resolution of infection or survival to cryptococcal infection.BALB/c mice or IL-17RA−/− mice received an intranasal inoculum of C. neoformans strain H99γ. Mice were assayed for survival through 35 days of primary infection with C. neoformans strain H99γ (A). Surviving mice were then challenged with C. neoformans strain H99 and assayed for survival through 28 days of secondary challenge (B). Culture of lung, spleen, and brain tissues at day 28 post-secondary challenge were determined from mice with positive cultures (C) and numbers of mice with positive cultures are shown above each bar. Survival data show one experiment containing nine WT and eight IL-17RA−/− mice. Asterisks (*) indicate where significant differences in fungal burden were observed in IL-17RA−/− mice compared to WT mice following infection with C. neoformans strain H99 (P<0.0001).
Mentions: Although antibody depletion significantly reduced the amount of IL-17A in lung homogenates, the depletion was not absolute. Therefore, we evaluated survival of IL-17 receptor A knock-out (IL-17RA−/−) mice given a pulmonary infection with C. neoformans strain H99γ. IL-17RA−/− mice still have the ability to produce IL-17A, but signaling through its receptor, IL-17RA, is abrogated [47]. Figure 6A demonstrates 100% survival of WT and IL-17RA−/− mice given a primary pulmonary infection with C. neoformans strain H99γ through day 35 post-inoculation. All surviving WT and IL-17RA−/−mice were subsequently re-challenged with the non-IFN-γ producing wild-type C. neoformans strain H99 on day 35 post-primary inoculation and also demonstrated 100% survival through day 28 post-secondary challenge (Figure 5B). Culture of tissue homogenates derived from re-challenged WT and IL-17RA−/− mice at day 28 post-secondary inoculation indicated no significant difference in fungal burden in lung or brain tissues (Figure 6C). Evidence of dissemination to the spleen was not observed in any surviving wild-type mice, but was observed in one surviving knock-out mouse. Interestingly, following differential plating on YPD media with and without nourseothricin (a selectable marker for the H99γ strain), colonization of spleen and brain was due to the challenge organism, strain H99, while the colonization of the lungs was due to the immunizing organism, strain H99γ. Our results suggest that IL-17A contributes to, but is not required for, the resolution of acute infection with C. neoformans strain H99γ. However, IL-17RA signaling may be needed to prevent dissemination of cryptococci from the lung to the CNS of immunized mice following re-challenge with WT cryptococci.

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