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  • 1. Howard, Jennifer
    et al.
    Loizon, Séverine
    Tyler, Christopher J.
    Duluc, Dorothée
    Moser, Bernhard
    Mechain, Matthieu
    Duvignaud, Alexandre
    Malvy, Denis
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Moreau, Jean-Francois
    Eberl, Matthias
    Mercereau-Puijalon, Odile
    Déchanet-Merville, Julie
    Behr, Charlotte
    Mamani-Matsuda, Maria
    The Antigen-Presenting Potential of V gamma 9V delta 2 T Cells During Plasmodium falciparum Blood-Stage Infection2017Ingår i: Journal of Infectious Diseases, ISSN 0022-1899, E-ISSN 1537-6613, Vol. 215, nr 10, s. 1569-1579Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    During Plasmodium falciparum infections, erythrocyte-stage parasites inhibit dendritic cell maturation and function, compromising effective antimalarial adaptive immunity. Human V gamma 9V delta 2 T cells can act in vitro as antigen-presenting cells (APCs) and induce alpha beta T-cell activation. However, the relevance of this activity in vivo has remained elusive. Because V gamma 9V delta 2 T cells are activated during the early immune response against P. falciparum infection, we investigated whether they could contribute to the instruction of adaptive immune responses toward malaria parasites. In P. falciparum-infected patients, V gamma 9V delta 2 T cells presented increased surface expression of APC-associated markers HLA-DR and CD86. In response to infected red blood cells in vitro, V gamma 9V delta 2 T cells upregulated surface expression of HLA-DR, HLA-ABC, CD40, CD80, CD83, and CD86, induced naive alpha beta T-cell responses, and cross-presented soluble prototypical protein to antigen-specific CD8(+) T cells. Our findings qualify V gamma 9V delta 2 T cells as alternative APCs, which could be harnessed for therapeutic interventions and vaccine design.

  • 2. McCall, Matthew B B
    et al.
    Hopman, Joost
    Daou, Modibo
    Maiga, Boubacar
    Dara, Victor
    Ploemen, Ivo
    Nganou-Makamdop, Krystelle
    Niangaly, Amadou
    Tolo, Youssouf
    Arama, Charles
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Bousema, J Teun
    van der Meer, Jos W
    van der Ven, André J A M
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Dolo, Amagana
    Doumbo, Ogobara K
    Sauerwein, Robert W
    Early interferon-gamma response against Plasmodium falciparum correlates with interethnic differences in susceptibility to parasitemia between sympatric Fulani and Dogon in Mali.2010Ingår i: Journal of Infectious Diseases, ISSN 0022-1899, E-ISSN 1537-6613, Vol. 201, nr 1, s. 142-52Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    INTRODUCTION: Interethnic differences in susceptibility to malaria provide a unique opportunity to explore immunological correlates of protection. The Fulani of Sahelian Africa are known for their reduced susceptibility to Plasmodium falciparum, compared with surrounding tribes, yet the immunology underlying this is still poorly understood. METHODS AND RESULTS: Here, we show that mononuclear cells from Fulani elicit >10-fold stronger interferon (IFN)-gamma production following a 24-h in vitro coincubation with asexual parasites than cells from sympatric Dogon. This response appears to be specific for P. falciparum among a panel of other human pathogens and is independent of the lower number of regulatory T cell counts present in Fulani. IFN-gamma responses in both tribes were inversely correlated with peripheral parasite density as quantified by nucleic acid sequenced-based amplification, but responses of Fulani remained significantly stronger than those of Dogon after adjustment for concurrent parasitemia, suggesting that hard-wired immunological differences underlie the observed protection. CONCLUSIONS: These results underscore the value of early IFN-gamma responses to P. falciparum as a correlate of anti-parasite immunity, not only in this setting but also in the wider context of malaria, and support the development of malaria vaccines aimed at inducing such responses.

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