CD8+ T-Cell Priming against a Nonsecreted Listeria monocytogenes Antigen Is Independent of the Antimicrobial Activities of Gamma Interferon

AUTOR(ES)

Tvinnereim, Amy R.

FONTE

American Society for Microbiology

RESUMO

Sublethal infection of mice with recombinant Listeria monocytogenes expressing a model epitope in either secreted or nonsecreted form results in similar CD8+ T-cell priming. Since nonsecreted bacterial proteins have no obvious access to the endogenous major histocompatibility complex (MHC) class I presentation pathway, presentation of these antigens requires destruction of the bacterium to reveal the nonsecreted molecules to an exogenous MHC class I presentation pathway. Gamma interferon (IFN-γ), a cytokine made by multiple cell types in response to L. monocytogenes infection, could be required for exogenous presentation of nonsecreted bacterial antigens via its capacity to upregulate the expression of molecules involved in antigen presentation, its capacity to activate macrophages to kill bacteria to expose nonsecreted molecules or both. IFN-γ knockout (KO) mice were used to address the requirement for IFN-γ in CD8+ T-cell priming against (i) a model exogenous antigen and (ii) secreted and nonsecreted L. monocytogenes antigens. We demonstrate that IFN-γ KO mice are capable of cross-presenting the model exogenous antigen ovalbumin to prime CD8+ T-cell responses that are only slightly weaker than that in wild-type (WT) mice. Despite their extreme susceptibility to primary L. monocytogenes infection, previously immunized and naive IFN-γ KO mice were able to generate CD8+ T-cell responses against both secreted and nonsecreted L. monocytogenes antigens which were similar to responses of WT mice. Interestingly, IFN-γ KO mice were as capable as WT mice in mediating the characteristic drop in bacterial load in the liver at 4 h postinfection, although the IFN-γ KO mice have exacerbated bacterial loads as early as 24 h postinfection. These results demonstrate that the regulatory functions of IFN-γ are not required for priming of CD8+ T cells by cross-presentation of a model exogenous antigen or in response to a nonsecreted L. monocytogenes antigen. In addition, the capacity of IFN-γ to activate the microbicidal activities of macrophages is not required for the very early innate immune response to L. monocytogenes or priming of CD8+ T cells against a nonsecreted bacterial antigen.

Documentos Relacionados

• Antigen sensitivity is a major determinant of CD8+ T-cell polyfunctionality and HIV-suppressive activity
• Immunodominance in Virus-Induced CD8+ T-Cell Responses Is Dramatically Modified by DNA Immunization and Is Regulated by Gamma Interferon†
• Evidence for CD8+ T-cell immunity to murine rotavirus in the absence of perforin, fas, and gamma interferon.
• CD8+-T-Cell Response to Secreted and Nonsecreted Antigens Delivered by Recombinant Listeria monocytogenes during Secondary Infection
• Application of the Intracellular Gamma Interferon Assay To Recalculate the Potency of CD8+ T-Cell Responses to Herpes Simplex Virus