Assuntos
Medicina Geral , Imunossupressores/uso terapêutico , Assistência de Longa Duração , Transplante de Órgãos , Atenção Primária à Saúde , Transplantados , Comorbidade , Medicina Geral/normas , Humanos , Imunossupressores/efeitos adversos , Assistência de Longa Duração/normas , Transplante de Órgãos/efeitos adversos , Transplante de Órgãos/normas , Polimedicação , Guias de Prática Clínica como Assunto , Atenção Primária à Saúde/normas , Fatores de Risco , Fatores de TempoRESUMO
BACKGROUND: Leukocyte Ig-like receptors (LILR) are a family of innate immune receptors with immunomodulatory functions. High-level expression of the receptors LILRB2 (ILT4) and LILRB4 (ILT3) is a feature of tolerogenic antigen presenting cells and has been observed in cancer and transplant situations. There are relatively few studies regarding these receptors in the context of infection and it is not yet clear how LILRB4 exerts its inhibitory effects. RESULTS: We studied the effects of LILRB4 ligation on antigen presenting cell phenotype, and the expression of LILRB2 and LILRB4 on Salmonella-infected antigen presenting cells. Ligation of LILRB4 throughout in vitro culture of dendritic cells led to an upregulation of the co-stimulatory protein CD86. Alterations in the production of IL-8 and IL-10 by LILRB4-ligated macrophages were also observed. Infection with Salmonella typhimurium or TLR stimulation with Salmonella components led to an upregulation of LILRB2 and LILRB4. CONCLUSION: Our results indicate that the inhibitory effects of LILRB4 do not result from a failure to upregulate co-stimulatory proteins. In addition to the high level expression that can render antigen presenting cells tolerogenic, there may be a role for lower level expression and activity of LILRB2 and LILRB4 in response to TLR signalling during an immune response to bacterial infection.
Assuntos
Glicoproteínas de Membrana/biossíntese , Receptores de Superfície Celular/metabolismo , Receptores Imunológicos/biossíntese , Infecções por Salmonella/imunologia , Salmonella typhimurium/imunologia , Células Apresentadoras de Antígenos/imunologia , Células Apresentadoras de Antígenos/metabolismo , Células Apresentadoras de Antígenos/patologia , Antígeno B7-2/biossíntese , Antígeno B7-2/genética , Antígeno B7-2/imunologia , Células Cultivadas , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Células Dendríticas/microbiologia , Células Dendríticas/patologia , Regulação para Baixo , Humanos , Imunofenotipagem , Interleucina-10/metabolismo , Interleucina-8/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/patologia , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/imunologia , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/imunologia , Receptores Imunológicos/genética , Receptores Imunológicos/imunologia , Infecções por Salmonella/genética , Infecções por Salmonella/metabolismo , Infecções por Salmonella/patologia , Salmonella typhimurium/patogenicidade , Regulação para CimaRESUMO
Leucocyte Ig-like receptors (LILR) are a family of innate immune receptors expressed on myeloid and lymphoid cells that influence adaptive immune responses. We identified a common mechanism of alternative mRNA splicing, which generates transcripts that encode soluble protein isoforms of the majority of human LILR. These alternative splice variants lack transmembrane and cytoplasmic encoding regions, due to the transcription of a cryptic stop codon present in an intron 5' of the transmembrane encoding exon. The alternative LILR transcripts were detected in cell types that express their membrane-associated isoforms. Expression of the alternative LILRB1 transcript in transfected cells resulted in the release of a soluble approximately 65 Kd LILRB1 protein into culture supernatants. Soluble LILRB1 protein was also detected in the culture supernatants of monocyte-derived DC. In vitro assays suggested that soluble LILRB1 could block the interaction between membrane-associated LILRB1 and HLA-class I. Soluble LILRB1 may act as a dominant negative regulator of HLA-class I-mediated LILRB1 inhibition. Soluble isoforms of the other LILR may function in a comparable way.
