The Pathology of Mycobacterium tuberculosis Infection

Abstract

Mycobacterium tuberculosis is an old enemy of the human race, with evidence of infection observed as early as 5000 years ago. Although more host-restricted than Mycobacterium bovis, which can infect all warm-blooded vertebrates, M. tuberculosis can infect, and cause morbidity and mortality in, several veterinary species as well. As M. tuberculosis is one of the earliest described bacterial pathogens, the literature describing this organism is vast and overwhelming. This review strives to distill what is currently known about this bacterium and the disease it causes for the veterinary pathologist.

Role of IL-10 and TNF-α during Mycobacterium tuberculosis infection in murine alveolar macrophages

“…Macrophages are critical in both permitting the survival of Mtb and in the innate and adaptive immune responses of the host (Russell, 2011;Sakamoto, 2012). They promote the T cell activation and recruitment crucial for containing Mtb within granulomas in the lung (Oxlade et al, 2009;Macdonald et al, 2012;Sakamoto, 2012).…”

“…Macrophages are critical in both permitting the survival of Mtb and in the innate and adaptive immune responses of the host (Russell, 2011;Sakamoto, 2012). They promote the T cell activation and recruitment crucial for containing Mtb within granulomas in the lung (Oxlade et al, 2009;Macdonald et al, 2012;Sakamoto, 2012). Macrophages can also produce cytokines and lipid mediators, which have been firmly established as key players in adaptive immunity, as both effectors and regulators, during Mtb infection (Oxlade et al, 2009;Russell, 2011).…”

“…During early infection stages, Mtb is phagocytosed by these cells, whose initial innate response can affect intracellular bacterial survival and proliferation. The potential molecular mechanism behind macrophage control of Mtb infection may involve the production of reactive nitrogen (RNI) and oxygen intermediates (ROI) and changes in phagolysosomal pH inducing apoptosis, among other factors (Cooper and Torrado, 2012;Sakamoto, 2012). In addition, the first cells to be infected release pro-inflammatory cytokines, including tumor necrosis factor (TNF)-a, interferon (IFN)-g, interleukin (IL)-10, IL-12, and IL-18, which exert various effects on macrophage functions and T cell responses (Cooper et al, 2011;Redford et al, 2011).…”

“…In contrast, immunosuppressive cytokines such as IL-10 and transforming growth factor (TGF)-b can inhibit macrophage functions, resulting in enhanced intracellular bacterial growth and reduction of nitric oxide production (Redford et al, 2011). Thus, the balance between TNF-a and IL-10 produced by macrophages against Mtb is thought to modulate induction of apoptosis during infection (Cooper et al, 2011;Sakamoto, 2012). As a transcription factor, signal transducer and activator of transcription 3 (STAT3) participates in many cytokine-related signaling pathways regulated by the suppressor of cytokine signaling family, in various cells and organs.…”

Perfil transcriptômico comparativo de macrófagos em cultura, infectados com isolados clínicos de Mycobacterium tuberculosis com diferentes perfis de resistência a quimioterápicos

“…Algumas cepas da M. tuberculosis com diferentes perfis de virulência são capazes de evadir dos mecanismos imune celulares, principalmente dos macrófagos, pela modulação de vias metabólicas de ativação dessas respostas ou ainda pela produção de proteínas protetoras, resultando em uma maior persistência/sucesso do bacilo na infecção (SAKAMOTO, 2012 tuberculosis, tanto pelo aumento da expressão de proteínas protetoras, como catalases e peroxidades (katG, ahpC, soda, sodC, noxR3), como pela produção de amônias que alcalinizam o meio, dentre outros (tabela 03) (MANCA et al, 1999;SHERMAN et al, 1996;DUSSURGET et al, 2001;RUAN et al, 1999).…”