RESUMO
New evidence has been emerging that antibodies can be protective in various experimental models of tuberculosis. Here, we report on protection against multidrug-resistant Mycobacterium tuberculosis (MDR-TB) infection using a combination of the human monoclonal IgA 2E9 antibody against the alpha-crystallin (Acr, HspX) antigen and mouse interferon-gamma in mice transgenic for the human IgA receptor, CD89. The effect of the combined mucosal IgA and IFN-γ; treatment was strongest (50-fold reduction) when therapy was applied at the time of infection, but a statistically significant reduction of lung bacterial load was observed even when the therapy was initiated once the infection had already been established. The protection involving enhanced phagocytosis and then neutrophil mediated killing of infected cells was IgA isotype mediated, because treatment with an IgG version of 2E9 antibody was not effective in human IgG receptor CD64 transgenic mice. The Acr antigen specificity of IgA antibodies for protection in humans has been indicated by their elevated serum levels in latent tuberculosis unlike the lack of IgA antibodies against the virulence-associated MPT64 antigen. Our results represent the first evidence for potential translation of mucosal immunotherapy for the management of MDR-TB.
Assuntos
Interferon gama/uso terapêutico , Pulmão/imunologia , Mycobacterium tuberculosis/fisiologia , Neutrófilos/imunologia , Mucosa Respiratória/imunologia , Tuberculose/terapia , Animais , Anticorpos Monoclonais/metabolismo , Antígenos de Bactérias/imunologia , Antígenos CD/genética , Antígenos CD/metabolismo , Carga Bacteriana , Proteínas de Bactérias/imunologia , Resistência a Múltiplos Medicamentos , Humanos , Imunoglobulina A/metabolismo , Pulmão/microbiologia , Camundongos , Camundongos Transgênicos , Mycobacterium tuberculosis/patogenicidade , Fagocitose , Receptores Fc/genética , Receptores Fc/metabolismo , Receptores de IgG/genética , Células THP-1 , Células U937 , alfa-Cristalinas/imunologiaRESUMO
IgA nephropathy (IgAN) is associated predominantly IgA deposition in the affected glomeruli and has been shown to be the most common glomerular disorder among young people in the world. Although the exact pathogenic mechanism underlying IgAN remains largely unknown, circulating IgA-containing immune complexes (IgA ICs) is considered to play a major role in initiating the development and evolution of the renal disorder. In this review article, we discuss the fundamental mechanisms of clearance kinetics of IgA ICs and related issues, covering the following: (1) role of circulating IgA ICs in the pathogenesis of IgAN and (2) elimination of IgA ICs from the body, with emphasis of the role of the liver and Fc receptors in immune cells.