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1.
Immunity ; 55(11): 1972-1974, 2022 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-36351370

RESUMO

Protecting the upper airways and brain from viral invasion through the olfactory mucosa is critical. Wellford et al. describe a barrier that restricts the passage of circulating antibodies and prevents them from reaching the olfactory mucosa. Instead, plasma cells are recruited into this site and prevent viral infection of the airways and the brain through local antibody production.


Assuntos
Plasmócitos , Sistema Respiratório , Encéfalo
2.
Eur J Immunol ; 53(5): e2350413, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36898761

RESUMO

Reexposure to a pathogen triggers the activation of memory T cells that have already encountered a similar microbe. These long-lived CD4 T cells either circulate through the blood and tissues or reside within organs and are referred to as tissue-resident T cells (CD4 TRM ). In the current issue of the European Journal of Immunology [Eur. J. Immunol. 2023. 53: 2250247] issue, Curham et al. found that tissue-resident memory CD4 T cells in the lung and nasal tissues can respond to noncognate immune challenges. CD4 TRM cells, which were formed in response to Bordetella pertussis, proliferated and produced IL-17A in response to a secondary challenge with heat-killed Klebsiella pneumonia or lipopolysaccharide (LPS). This bystander response depends on the presence of dendritic cells that provide inflammatory cytokines. Furthermore, post K. pneumonia, intranasal immunization with whole cell pertussis vaccine reduced bacterial burden in the nasal tissue in a CD4 T-cell-dependent manner. The study indicates that the noncognate activation of TRM may serve as an innate-like immune response that rapidly develops before establishing a new pathogen-specific adaptive immune response.


Assuntos
Linfócitos T CD4-Positivos , Células T de Memória , Humanos , Amigos , Bordetella pertussis , Vacina contra Coqueluche , Memória Imunológica
3.
Eur J Immunol ; 51(12): 2708-3145, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34910301

RESUMO

The third edition of Flow Cytometry Guidelines provides the key aspects to consider when performing flow cytometry experiments and includes comprehensive sections describing phenotypes and functional assays of all major human and murine immune cell subsets. Notably, the Guidelines contain helpful tables highlighting phenotypes and key differences between human and murine cells. Another useful feature of this edition is the flow cytometry analysis of clinical samples with examples of flow cytometry applications in the context of autoimmune diseases, cancers as well as acute and chronic infectious diseases. Furthermore, there are sections detailing tips, tricks and pitfalls to avoid. All sections are written and peer-reviewed by leading flow cytometry experts and immunologists, making this edition an essential and state-of-the-art handbook for basic and clinical researchers.


Assuntos
Doenças Autoimunes/imunologia , Citometria de Fluxo , Infecções/imunologia , Neoplasias/imunologia , Animais , Doença Crônica , Humanos , Camundongos , Guias de Prática Clínica como Assunto
4.
Proc Natl Acad Sci U S A ; 116(15): 7425-7430, 2019 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-30910977

RESUMO

Serum IgG, which is mainly generated from IgG-secreting plasma cells in the bone marrow (BM), protects our body against various pathogens. We show here that the protein SiiE of Salmonella is both required and sufficient to prevent an efficient humoral immune memory against the pathogen by selectively reducing the number of IgG-secreting plasma cells in the BM. Attenuated SiiE-deficient Salmonella induces high and lasting titers of specific and protective Salmonella-specific IgG and qualifies as an efficient vaccine against Salmonella A SiiE-derived peptide with homology to laminin ß1 is sufficient to ablate IgG-secreting plasma cells from the BM, identifying laminin ß1 as a component of niches for IgG-secreting plasma cells in the BM, and furthermore, qualifies it as a unique therapeutic option to selectively ablate IgG-secreting plasma cells in autoimmune diseases and multiple myeloma.


Assuntos
Células da Medula Óssea/imunologia , Imunidade Humoral , Imunoglobulina G/imunologia , Memória Imunológica , Plasmócitos/imunologia , Salmonella/imunologia , Animais , Células da Medula Óssea/citologia , Imunoglobulina G/genética , Laminina/genética , Laminina/imunologia , Camundongos , Camundongos Knockout , Plasmócitos/citologia , Salmonella/genética
5.
Cells ; 11(9)2022 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-35563853

RESUMO

Memory plasma cells constitutively produce copious amounts of antibodies, imposing a critical risk factor for autoimmune disease. We previously found that plasma cell survival requires secreted factors such as APRIL and direct contact to stromal cells, which act in concert to activate NF-κB- and PI3K-dependent signaling pathways to prevent cell death. However, the regulatory properties of the underlying biochemical network are confounded by the complexity of potential interaction and cross-regulation pathways. Here, based on flow-cytometric quantification of key signaling proteins in the presence or absence of the survival signals APRIL and contact to the stromal cell line ST2, we generated a quantitative model of plasma cell survival. Our model emphasizes the non-redundant nature of the two plasma cell survival signals APRIL and stromal cell contact, and highlights a requirement for differential regulation of individual caspases. The modeling approach allowed us to unify distinct data sets and derive a consistent picture of the intertwined signaling and apoptosis pathways regulating plasma cell survival.


Assuntos
Fosfatidilinositol 3-Quinases , Plasmócitos , Apoptose/fisiologia , Caspases/metabolismo , Modelos Teóricos , Plasmócitos/metabolismo
6.
Curr Opin Immunol ; 71: 97-102, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34303157

RESUMO

Memory plasma cells, also called long-lived plasma cells, provide 'humoral immunity' by continued secretion of protective antibodies against pathogens, which the immune system has once encountered. They are maintained mainly in the bone marrow, docking on to stromal cells individually. In those niches they can apparently persist for decades (Chang et al., 2018 [1]). Integrin-mediated contact to the stromal cell provides an essential survival signal to the plasma cell, activating the PI3K signalling pathway, downregulating FoxO1/3a and repressing the activation of caspases 3 and 7. In a redundant form, the cytokines BAFF and APRIL, ligands of the plasma cell receptors TACI and BCMA, provide a second essential survival signal, preventing activation of caspase 12, as triggered by endoplasmic reticulum stress.


Assuntos
Anticorpos/imunologia , Fator Ativador de Células B/imunologia , Plasmócitos/imunologia , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/imunologia , Estresse do Retículo Endoplasmático/imunologia , Humanos
7.
Cell Rep ; 32(5): 107982, 2020 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-32755576

RESUMO

The persistence of long-lived memory plasma cells in the bone marrow depends on survival factors available in the bone marrow, which are provided in niches organized by stromal cells. Using an ex vivo system in which we supply the known survival signals, direct cell contact to stromal cells, and the soluble cytokine a proliferation-inducing ligand (APRIL), we have elucidated the critical signaling pathways required for the survival of long-lived plasma cells. Integrin-mediated contact of bone marrow plasma cells with stromal cells activates the phosphatidylinositol 3-kinase (PI3K) signaling pathway, leading to critical inactivation of Forkhead-Box-Protein O1/3 (FoxO1/3) and preventing the activation of mitochondrial stress-associated effector caspases 3 and 7. Accordingly, inhibition of PI3K signaling in vivo ablates bone marrow plasma cells. APRIL signaling, by the nuclear factor κB (NF-κB) pathway, blocks activation of the endoplasmic-reticulum-stress-associated initiator caspase 12. Thus, stromal-cell-contact-induced PI3K and APRIL-induced NF-κB signaling provide the necessary and complementary signals to maintain bone marrow memory plasma cells.


Assuntos
Estresse do Retículo Endoplasmático , Memória Imunológica , Mitocôndrias/metabolismo , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Plasmócitos/citologia , Plasmócitos/imunologia , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/metabolismo , Animais , Células da Medula Óssea/metabolismo , Caspases/metabolismo , Morte Celular , Sobrevivência Celular , Regulação para Baixo , Proteína Forkhead Box O1/metabolismo , Proteína Forkhead Box O3/metabolismo , Fatores Reguladores de Interferon/metabolismo , Camundongos Endogâmicos C57BL , Transdução de Sinais , Células Estromais/metabolismo
8.
Nat Commun ; 11(1): 2570, 2020 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-32444631

RESUMO

At present, it is not clear how memory B lymphocytes are maintained over time, and whether only as circulating cells or also residing in particular tissues. Here we describe distinct populations of isotype-switched memory B lymphocytes (Bsm) of murine spleen and bone marrow, identified according to individual transcriptional signature and B cell receptor repertoire. A population of marginal zone-like cells is located exclusively in the spleen, while a population of quiescent Bsm is found only in the bone marrow. Three further resident populations, present in spleen and bone marrow, represent transitional and follicular B cells and B1 cells, respectively. A population representing 10-20% of spleen and bone marrow memory B cells is the only one qualifying as circulating. In the bone marrow, all cells individually dock onto VCAM1+ stromal cells and, reminiscent of resident memory T and plasma cells, are void of activation, proliferation and mobility.


Assuntos
Linfócitos B/imunologia , Células da Medula Óssea/imunologia , Switching de Imunoglobulina , Memória Imunológica , Baço/imunologia , Adjuvantes Imunológicos/farmacologia , Animais , Animais Selvagens/imunologia , Linfócitos B/citologia , Linfócitos B/efeitos dos fármacos , Células da Medula Óssea/citologia , Ciclo Celular , Proliferação de Células/genética , Regulação da Expressão Gênica/imunologia , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Receptores de Antígenos de Linfócitos B/genética , Receptores de Antígenos de Linfócitos B/imunologia , Baço/citologia , Células Estromais/citologia , Molécula 1 de Adesão de Célula Vascular/metabolismo
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