title: B and T lymphocyte attenuator restricts the protective immune response against experimental malaria.
abstract: The immune response against the blood stage of malaria has to be tightly regulated to allow for vigorous antiplasmodial activity while restraining potentially lethal immunopathologic damage to the host like cerebral malaria. Coinhibitory cell surface receptors are important modulators of immune activation. B and T lymphocyte attenuator (BTLA) (CD272) is a coinhibitory receptor expressed by most leukocytes, with the highest expression levels on T and B cells, and is involved in the maintenance of peripheral tolerance by dampening the activation of lymphocytes. The function of BTLA is described in several models of inflammatory disorders and autoimmunity, but its function in infectious diseases is less well characterized. Also, little is known about the influence of BTLA on non-T cells. In this study, we analyzed the function of BTLA during blood-stage malaria infection with the nonlethal Plasmodium yoelii strain 17NL. We show that BTLA knockout mice exhibit strongly reduced parasitemia and clear the infection earlier compared with wild-type mice. This increased resistance was seen before the onset of adaptive immune mechanisms and even in the absence of T and B cells but was more pronounced at later time points when activation of T and B cells was observed. We demonstrate that BTLA regulates production of proinflammatory cytokines in a T cell-intrinsic way and B cell intrinsically regulates the production of P. yoelii 17NL-specific Abs. These results indicate that the coinhibitory receptor BTLA plays a critical role during experimental malaria and attenuates the innate as well as the subsequent adaptive immune response.
authors: Department of Immunology, Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany.
authors: Guido
authors: G
authors: Adler
authors: Christiane
authors: C
authors: Steeg
authors: Klaus
authors: K
authors: Pfeffer
authors: Theresa L
authors: TL
authors: Murphy
authors: Kenneth M
authors: KM
authors: Murphy
authors: Jean
authors: J
authors: Langhorne
authors: Thomas
authors: T
authors: Jacobs
mesh_terms: D056704:Adaptive Immunity / Q000235:genetics; D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis / Q000502:physiology; D004195:Disease Models, Animal; D060467:Disease Resistance / Q000235:genetics; D007113:Immunity, Innate / Q000235:genetics; D018836:Inflammation Mediators / Q000378:metabolism / Q000502:physiology; D016779:Malaria, Cerebral / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D018512:Parasitemia / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control; D010967:Plasmodium yoelii / Q000276:immunology; D011828:Radiation Chimera / Q000235:genetics / Q000276:immunology; D011971:Receptors, Immunologic / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; C488868:BTLA protein, mouse; D016207:Cytokines; D018836:Inflammation Mediators; D011971:Receptors, Immunologic