HLA class II (DR0401) molecules induce Foxp3+ regulatory T cell suppression of B cells in Plasmodium yoelii strain 17XNL malaria

Wathsala Wijayalath, Rebecca Danner, Yuliya Kleschenko, Sai Majji, Eileen Franke Villasante, Thomas L. Richie, Teodor Doru Brumeanu, Chella S. David, Sofia Casares

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Unlike human malaria parasites that induce persistent infection, some rodent malaria parasites, like Plasmodium yoelii strain 17XNL (Py17XNL), induce a transient (self-curing) malaria infection. Cooperation between CD4 T cells and B cells to produce antibodies is thought to be critical for clearance of Py17XNL parasites from the blood, with major histocompatibility complex (MHC) class II molecules being required for activation of CD4 T cells. In order to better understand the correspondence between murine malaria models and human malaria, and in particular the role of MHC (HLA) class II molecules, we studied the ability of humanized mice expressing human HLA class II molecules to clear Py17XNL infection. We showed that humanized mice expressing HLA-DR4 (DR0401) molecules and lacking mouse MHC class II molecules (EA0) have impaired production of specific antibodies to Py17XNL and cannot cure the infection. In contrast, mice expressing HLA-DR4 (DR0402), HLA-DQ6 (DQ0601), HLA-DQ8 (DQ0302), or HLA-DR3 (DR0301) molecules in an EA0 background were able to elicit specific antibodies and self-cure the infection. In a series of experiments, we determined that the inability of humanized DR0401.EA0 mice to elicit specific antibodies was due to expansion and activation of regulatory CD4+ Foxp3+ T cells (Tregs) that suppressed B cells to secrete antibodies through cell-cell interactions. Treg depletion allowed the DR0401.EA0 mice to elicit specific antibodies and self-cure the infection. Our results demonstrated a differential role of MHC (HLA) class II molecules in supporting antibody responses to Py17XNL malaria and revealed a new mechanism by which malaria parasites stimulate B cell-suppressogenic Tregs that prevent clearance of infection.

Original languageEnglish (US)
Pages (from-to)286-297
Number of pages12
JournalInfection and Immunity
Volume82
Issue number1
DOIs
StatePublished - Jan 1 2014

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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    Wijayalath, W., Danner, R., Kleschenko, Y., Majji, S., Villasante, E. F., Richie, T. L., Brumeanu, T. D., David, C. S., & Casares, S. (2014). HLA class II (DR0401) molecules induce Foxp3+ regulatory T cell suppression of B cells in Plasmodium yoelii strain 17XNL malaria. Infection and Immunity, 82(1), 286-297. https://doi.org/10.1128/IAI.00272-13