Major Histocompatibility Complex Class II-Restricted, CD4+ T Cell-Dependent and -Independent Mechanisms Are Required for Vaccine-Induced Protective Immunity against Coxiella burnetii

Copyright © 2020 American Society for Microbiology..

To understand the role of major histocompatibility complex class I (MHC-I) and MHC-II in vaccine-mediated protection against Coxiella burnetii, we evaluated the protective efficacy of a formalin-inactivated C. burnetii Nine Mile phase I vaccine (PIV) in β2-microglobulin-deficient (B2m KO) and MHC-II-deficient (MHC-II KO) mice. Vaccination reduced disease severity in wild-type (WT) and B2m KO mice but failed to reduce bacterial burden in MHC-II KO mice. This suggests that the MHC-II antigen presentation pathway is required for PIV-mediated protection against C. burnetii infection. MHC-I and MHC-II affect antibody isotype switching, since both PIV-vaccinated B2m KO and MHC-II KO mice produced less Coxiella-specific IgG than PIV-vaccinated WT mice. Interestingly, MHC-II and CD4 deficiencies were not equivalent in terms of splenomegaly and bacterial clearance. This demonstrates a partial role for CD4+ T cells while revealing MHC-II-restricted, CD4-independent mechanisms. Adoptive transfer of CD4+ T cells from PIV-vaccinated WT mice to naive CD4-deficient (CD4 KO) mice demonstrated that antigen-experienced CD4+ T cells are sufficient to generate protection. Conversely, transfer of naive CD4+ T cells to PIV-vaccinated CD4 KO mice exacerbates disease. Using Tbet-deficient (Tbet KO) mice, we showed a partial role for Th1 subset CD4+ T cells in vaccine protection. Furthermore, Th1-independent roles for Tbet were suggested by significant differences in disease between PIV-vaccinated Tbet KO and CD4 KO mice. Interferon gamma was shown to contribute to the host inflammatory response but not bacterial clearance. Collectively, these findings suggest that vaccine-induced protective immunity against a murine model of experimental Q fever requires MHC-II-restricted, CD4+ T cell-dependent and -independent mechanisms that can be exploited for a new-generation human Q fever vaccine.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:88

Enthalten in:

Infection and immunity - 88(2020), 3 vom: 20. Feb.

Sprache:

Englisch

Beteiligte Personen:

Ledbetter, Lindsey [VerfasserIn]
Cherla, Rama [VerfasserIn]
Chambers, Catherine [VerfasserIn]
Zhang, Yan [VerfasserIn]
Mitchell, William J [VerfasserIn]
Zhang, Guoquan [VerfasserIn]

Links:

Volltext

Themen:

82115-62-6
Antigens, Bacterial
Bacterial Vaccines
CD4+ T cells
CD4 Antigens
Coxiella burnetii
Histocompatibility Antigens Class II
IFN-γ
Immunoglobulin G
Interferon-gamma
Journal Article
Major histocompatibility complex
Research Support, N.I.H., Extramural
Tbet-deficient mice
Th1 response
Vaccine-induced immunity
Vaccines, Inactivated

Anmerkungen:

Date Completed 23.04.2020

Date Revised 21.08.2020

published: Electronic-Print

Citation Status MEDLINE

doi:

10.1128/IAI.00824-19

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM30394062X