دورية أكاديمية
أعرض في EDS

Adjuvant Pam3CSk4 does not improve the immunization against Cryptococcus gattii infection in C57BL/6 mice.

التفاصيل البيبلوغرافية
العنوان: Adjuvant Pam3CSk4 does not improve the immunization against Cryptococcus gattii infection in C57BL/6 mice.
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.)
References: J Immunol. 2001 Apr 1;166(7):4620-6. (PMID: 11254720)
Front Cell Infect Microbiol. 2016 Jan 06;5:101. (PMID: 26779451)
mBio. 2015 Oct 13;6(5):e01340-15. (PMID: 26463162)
Infect Immun. 2010 Sep;78(9):3861-70. (PMID: 20547742)
Infect Immun. 2004 Sep;72(9):5373-82. (PMID: 15322035)
Vaccines (Basel). 2022 Apr 15;10(4):. (PMID: 35455369)
Immunity. 2010 May 28;32(5):692-702. (PMID: 20434372)
Nature. 2000 Aug 17;406(6797):782-7. (PMID: 10963608)
Mucosal Immunol. 2018 Nov;11(6):1763-1776. (PMID: 30127384)
PLoS One. 2014 Aug 13;9(8):e104316. (PMID: 25119981)
J Biol Chem. 2001 Jun 22;276(25):22041-7. (PMID: 11285258)
J Immunol. 2003 Jul 1;171(1):417-25. (PMID: 12817025)
Antimicrob Agents Chemother. 2005 Mar;49(3):952-8. (PMID: 15728888)
Eur J Immunol. 2014 Dec;44(12):3596-604. (PMID: 25187063)
J Immunol. 2007 Jun 1;178(11):6715-9. (PMID: 17513716)
Methods Mol Biol. 2009;470:71-83. (PMID: 19089377)
Infect Dis Clin North Am. 2002 Dec;16(4):837-74, v-vi. (PMID: 12512184)
Clin Microbiol Rev. 2012 Jul;25(3):387-408. (PMID: 22763631)
Infect Immun. 1998 Jun;66(6):2632-9. (PMID: 9596727)
J Immunol. 2002 Nov 1;169(9):4905-12. (PMID: 12391202)
Infect Immun. 2015 Apr;83(4):1577-86. (PMID: 25644007)
PLoS One. 2013;8(1):e55579. (PMID: 23383232)
Structure. 2011 Apr 13;19(4):447-59. (PMID: 21481769)
J Fungi (Basel). 2018 Mar 07;4(1):. (PMID: 29518906)
mBio. 2013 Jun 18;4(3):e00264-13. (PMID: 23781069)
PLoS One. 2013 Aug 05;8(8):e71185. (PMID: 23940714)
Front Immunol. 2014 Sep 25;5:461. (PMID: 25309543)
mBio. 2015 Dec 22;6(6):e01905-15. (PMID: 26695631)
Front Cell Infect Microbiol. 2020 Feb 11;10:37. (PMID: 32117810)
Antimicrob Agents Chemother. 1998 Jun;42(6):1437-46. (PMID: 9624491)
Biochem Soc Trans. 2007 Dec;35(Pt 6):1437-44. (PMID: 18031241)
Infect Immun. 1994 May;62(5):1507-12. (PMID: 8168912)
Microbes Infect. 2019 Aug - Sep;21(7):328-335. (PMID: 30817996)
Vaccine. 2011 Sep 2;29(38):6641-9. (PMID: 21742006)
J Med Microbiol. 2000 Aug;49(8):733-737. (PMID: 10933259)
Trends Immunol. 2004 Dec;25(12):677-86. (PMID: 15530839)
Infect Immun. 2014 Sep;82(9):3880-90. (PMID: 24980974)
J Infect Dis. 2003 Jul 1;188(1):165-72. (PMID: 12825186)
PeerJ. 2020 Nov 25;8:e10295. (PMID: 33304649)
Curr Clin Microbiol Rep. 2017 Jun;4(2):88-95. (PMID: 29130027)
J Cell Physiol. 2018 Sep;233(9):6425-6440. (PMID: 29319160)
Immunity. 2010 May 28;32(5):593-604. (PMID: 20510870)
Front Immunol. 2019 Jan 29;10:66. (PMID: 30761136)
J Immunol. 2000 Dec 1;165(11):6538-44. (PMID: 11086096)
J Infect Chemother. 2015 Dec;21(12):831-6. (PMID: 26477011)
EBioMedicine. 2021 Jan;63:103153. (PMID: 33279857)
Sci Rep. 2017 Aug 1;7(1):7083. (PMID: 28765651)
Front Immunol. 2018 Apr 04;9:651. (PMID: 29670625)
PLoS One. 2013 Dec 12;8(12):e80743. (PMID: 24349012)
J Biol Chem. 2007 Jul 20;282(29):21145-59. (PMID: 17462991)
PLoS One. 2011 Feb 17;6(2):e17204. (PMID: 21359196)
Vaccine. 2008 Sep 2;26(37):4866-75. (PMID: 18455278)
Infect Immun. 2002 May;70(5):2598-604. (PMID: 11953401)
Pathog Dis. 2016 Jun;74(4):ftw020. (PMID: 27001975)
Eur J Immunol. 2005 Mar;35(3):870-8. (PMID: 15714580)
J Immunol. 2013 Jul 1;191(1):249-61. (PMID: 23740956)
Vaccine. 2008 Oct 16;26(44):5662-7. (PMID: 18675866)
Innate Immun. 2020 Feb;26(2):117-129. (PMID: 31446837)
Nat Rev Immunol. 2010 Jun;10(6):384. (PMID: 20514675)
J Immunol. 2016 Jan 1;196(1):365-74. (PMID: 26590316)
Infect Immun. 2002 Jan;70(1):240-8. (PMID: 11748189)
Mol Pharm. 2012 Sep 4;9(9):2710-8. (PMID: 22823162)
AIDS. 2009 Feb 20;23(4):525-30. (PMID: 19182676)
Annu Rev Immunol. 2010;28:445-89. (PMID: 20192806)
mBio. 2019 Nov 26;10(6):. (PMID: 31772051)
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
الوصف
تدمد:2167-8359
DOI:10.7717/peerj.14778