دورية أكاديمية
Adjuvant Pam3CSk4 does not improve the immunization against Cryptococcus gattii infection in C57BL/6 mice.
العنوان: | Adjuvant Pam3CSk4 does not improve the immunization against Cryptococcus gattii infection in C57BL/6 mice. |
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المؤلفون: | de Campos GY; Department of Cell and Molecular Biology and Pathogenic Bioagents, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil., Oliveira-Brito PKM; Department of Cell and Molecular Biology and Pathogenic Bioagents, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil., Guimarães JG; Department of Cell and Molecular Biology and Pathogenic Bioagents, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil., da Costa LS; Department of Microbiology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil., Lazo Chica JE; Institute of Natural and Biological Sciences, Federal University of Triângulo Mineiro, Uberaba, Minas Gerais, Brazil., da Silva TA; Department of Cell and Molecular Biology and Pathogenic Bioagents, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil. |
المصدر: | PeerJ [PeerJ] 2023 Jan 31; Vol. 11, pp. e14778. Date of Electronic Publication: 2023 Jan 31 (Print Publication: 2023). |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: PeerJ Inc Country of Publication: United States NLM ID: 101603425 Publication Model: eCollection Cited Medium: Internet ISSN: 2167-8359 (Electronic) Linking ISSN: 21678359 NLM ISO Abbreviation: PeerJ Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Corte Madera, CA : PeerJ Inc. |
مواضيع طبية MeSH: | Cryptococcosis*/prevention & control , Cryptococcus gattii*, Animals ; Mice ; Interleukin-17 ; Toll-Like Receptor 2 ; Mice, Inbred C57BL ; Immunization ; Vaccination ; Adjuvants, Immunologic/pharmacology |
مستخلص: | Background: Cryptococcosis is a relevant invasive fungal infection that affects immunocompromised and immunocompetent individuals when caused by Cryptococcus gattii . Host innate and adaptive immune responses can be subverted by C. gattii, that blocks the differentiation of T helper (Th) 1 and Th17 cells, which are involved in the protection against cryptococcosis. Moreover, the macrophage polarization is modulated by C. gattii infection that requires a balance in the macrophage subsets to control the C. gattii infection. Toll-like receptor (TLR) 2 agonists are important immunomodulators favoring a pro-inflammatory response with potential fungicidal activity, and TLR2 agonists have been used as adjuvants in vaccines against infections caused by bacteria or viruses. Therefore, this work aimed to evaluate the immunomodulatory effect of the tripalmitoyl lipopeptide S-glycerol cysteine (Pam3CSK4 or P3C4), a TLR2 agonist, as an adjuvant in the vaccination against C. gattii infection. Methods and Results: C57BL/6 mice were immunized with 2 × 10 7 inactivated yeasts of C. gattii via intranasal route on day 1, 14 and 28 (Immunized group). Immunization was associated with 1µg or 10µg of adjuvant P3C4 (Immunized+P3C4-1µg or Immunized+P3C4-10 µg), followed by C. gattii infection on day 42 after the immunization protocol. Immunized+P3C4-1 µg group had reduced levels of IgG1, IgG2a and IgA and no significant difference in the IgG and IgM anti-GXM antibody titer was detected, compared to the Immunized group. High levels of IL-17 and IL-1 β in lung tissue of mice from the Immunized+P3C4-1µg group did not promote a predominance of Th17 cells, in contrast, the frequency of TLR2 + cells was increased in immunized mice that received 1 µg of P3C4. The reduction in the relative expression of T-bet and high levels of Foxp3 detected in the lungs of the Immunized+P3C4-1µg group suggest a prevalence of regulatory T cells in the tissue, which did not contribute to the control of C. gattii infection. The immunization protocol associated with 10 µg of adjuvant P3C4 induced high levels of IL-17 in the lung tissue, whereas the levels of pro-inflammatory cytokines were downregulated. To evaluate the effect of adjuvant P3C4 in the control of C. gattii infection, quantification of the fungal burden in the lungs was performed by the CFU assay, and the groups with adjuvant P3C4 showed a pulmonary C. gattii burden that was not significantly altered when compared with the immunized group. The mice that received 1 µg of adjuvant P3C4 had a lower percentage of inflammatory infiltrate in the lungs. Conclusion: The immunomodulatory effect of P3C4, associated with the immunization protocol, plays an imbalance between pro- and anti-inflammatory response in the lungs that did not favor a protection against C. gattii infection, which is related to the immune response characterized by a suppressive/regulatory profile in the pulmonary microenvironment after C. gattii infection. Competing Interests: The authors declare there are no competing interests. (©2023 de Campos et al.) |
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فهرسة مساهمة: | Keywords: Cryptococcus gattii; Immunomodulation; Pam3CSK4; TLR2; Vaccine |
المشرفين على المادة: | 0 (Interleukin-17) 0 (Toll-Like Receptor 2) 0 (Adjuvants, Immunologic) |
تواريخ الأحداث: | Date Created: 20230206 Date Completed: 20230207 Latest Revision: 20230428 |
رمز التحديث: | 20230429 |
مُعرف محوري في PubMed: | PMC9897066 |
DOI: | 10.7717/peerj.14778 |
PMID: | 36743957 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2167-8359 |
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DOI: | 10.7717/peerj.14778 |