RESUMO
Post-injury dysfunction of humoral immunity accounts for infections and poor outcomes in cardiovascular diseases. Among immunoglobulins (Ig), IgA, the most abundant mucosal antibody, is produced by plasma B cells in intestinal Peyer's patches (PP) and lamina propria. Here we show that patients with stroke and myocardial ischemia (MI) had strongly reduced IgA blood levels. This was phenocopied in experimental mouse models where decreased plasma and fecal IgA were accompanied by rapid loss of IgA-producing plasma cells in PP and lamina propria. Reduced plasma IgG was detectable in patients and experimental mice 3-10 d after injury. Stroke/MI triggered the release of neutrophil extracellular traps (NETs). Depletion of neutrophils, NET degradation or blockade of NET release inhibited the loss of IgA+ cells and circulating IgA in experimental stroke and MI and in patients with stroke. Our results unveil how tissue-injury-triggered systemic NET release disrupts physiological Ig secretion and how this can be inhibited in patients.
Assuntos
Armadilhas Extracelulares , Infarto do Miocárdio , Neutrófilos , Armadilhas Extracelulares/metabolismo , Armadilhas Extracelulares/imunologia , Humanos , Animais , Infarto do Miocárdio/imunologia , Infarto do Miocárdio/patologia , Infarto do Miocárdio/metabolismo , Masculino , Neutrófilos/imunologia , Neutrófilos/metabolismo , Feminino , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Acidente Vascular Cerebral/imunologia , Acidente Vascular Cerebral/patologia , Acidente Vascular Cerebral/metabolismo , Nódulos Linfáticos Agregados/imunologia , Nódulos Linfáticos Agregados/patologia , Nódulos Linfáticos Agregados/metabolismo , Imunoglobulina A/metabolismo , Imunoglobulina A/imunologia , Imunoglobulina A/sangue , Idoso , Pessoa de Meia-Idade , Imunoglobulina G/imunologia , Imunoglobulina G/metabolismo , Imunidade Humoral , Estudos de Casos e Controles , Camundongos , Plasmócitos/imunologia , Plasmócitos/metabolismoRESUMO
Stroke is primarily a neurodegenerative disease but can also severely impact the functions of other vital organs and deteriorate disease outcomes. A malfunction of the gastrointestinal tract (GIT), commonly observed in stroke patients, is often characterized by severe bowel obstruction, intestinal microbiota changes and inflammation. Over-activated immune cells after stroke are the major contributors to endorse intestinal inflammation and may induce damage to single-layer epithelial cell barriers. The post-stroke leakage of intestinal barriers may allow the translocation and dissemination of resident microflora to systemic organs and cause sepsis. This overshooting systemic immune reaction fuels ongoing inflammation in the degenerating brain and slows recovery. Currently, the therapeutic options to treat these GIT-associated anomalies are very limited and further research is required to develop novel treatments. In this mini-review, we first discuss the current knowledge from clinical studies and experimental stroke models that provide strong evidence of the existence of post-stroke GIT complications. Then, we review the literature regarding novel therapeutic approaches that might help to maintain GIT homeostasis and improve neurological outcomes in stroke patients.