Trans‐species communication in the <i><scp>M</scp>ycobacterium tuberculosis‐</i>infected macrophage

Tan, Shumin; Russell, David G.

doi:10.1111/imr.12254

Cited by 31 publications

(21 citation statements)

References 121 publications

(224 reference statements)

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“…In response to the capability of host cells to eliminate them, pathogenic mycobacteria have evolved mechanisms for the manipulation of the host immune response by secretion of virulence factors through specialized secretion systems (Baxt et al, 2013;Houben et al, 2013). The bacteria are able to prevent lysosomal fusion and acidification of phagosomal compartments (Armstrong and Hart, 1971;Tan and Russell, 2015). Although a fraction of Mtb within a host cell is kept inside phagosomes, another fraction is able to escape from the phagosomes into the cytoplasm (van der Wel et al, 2007;Simeone et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Efferocytosis and extrusion of leukocytes determine the progression of early mycobacterial pathogenesis

Hosseini

Lamers

Soltani

et al. 2016

Journal of Cell Science

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Macrophages and neutrophils are the first responders to invading pathogens and contribute strongly to the host defense against intracellular pathogens. The collective interplay and dynamic interactions between these leukocytes are to a large extent not understood. In the present study, we have investigated their role using a combination of confocal laser-scanning and electron microscopy in a zebrafish model for tuberculosis, a local Mycobacterium marinum infection in the tissue of the larval tail fin. Our results show that neutrophils are efficient in phagocytosis of mycobacteria and that they contribute largely to their dissemination. Macrophages appear to play a major role in efferocytosis, phagocytosis of dead cells that contain bacterial content. Phagocytic cells with large bacterial aggregates are formed that can be extruded out of the tissue after cell death. Alternatively, these excessively infected cells can undergo necrosis leading to immediate recruitment of surrounding leukocytes and subsequent phagocytosis of released bacteria. Our data show that these necrotic burst events result in progression of the infection, whereas extrusion abates the infection.

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Section: Introductionmentioning

confidence: 99%

Efferocytosis and extrusion of leukocytes determine the progression of early mycobacterial pathogenesis

Hosseini

Lamers

Soltani

et al. 2016

Journal of Cell Science

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“…Owing to the central role of the macrophage as host and effector cell during M . tuberculosis infection [ 43 , 44 ], many studies have been centered in macrophage cell cultures. In terms of human-based systems, monocyte-derived macrophages are the most widely used culture.…”

Section: Human-based In Vitro Models In Tb Researchmentioning

confidence: 99%

Experimental study of tuberculosis: From animal models to complex cell systems and organoids

et al. 2017

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Tuberculosis (TB) is a devastating disease to mankind that has killed more people than any other infectious disease. Despite many efforts and successes from the scientific and health communities, the prospect of TB elimination remains distant. On the one hand, sustainable public health programs with affordable and broad implementation of anti-TB measures are needed. On the other hand, achieving TB elimination requires critical advances in three areas: vaccination, diagnosis, and treatment. It is also well accepted that succeeding in advancing these areas requires a deeper knowledge of host—pathogen interactions during infection, and for that, better experimental models are needed. Here, we review the potential and limitations of different experimental approaches used in TB research, focusing on animal and human-based cell culture models. We highlight the most recent advances in developing in vitro 3D models and introduce the potential of lung organoids as a new tool to study Mycobacterium tuberculosis infection.

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“…Furthermore, Mtb is able to direct fatty acid metabolites toward pathways that prevent their toxic accumulation within the granuloma [ 11 ]. Cholesterol esters are typically produced by foamy macrophages; thus, their presence in granulomas is indicative of a degenerative process which may lead to cell death and contribute to the development of caseous necrosis [ 112 ]. Labeling of macrophage with proprionate, oleate, and stearate within lipid droplets prior to infection demonstrated that Mtb has access to and incorporates host fatty acids into its cell wall lipids [ 11 ].…”

Section: The Granuloma As An Interface For Metabolism and Immunitymentioning

confidence: 99%

Host-directed therapy targeting the Mycobacterium tuberculosis granuloma: a review

et al. 2015

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Infection by the intracellular bacterial pathogen Mycobacterium tuberculosis (Mtb) is a major cause of morbidity and mortality worldwide. Slow progress has been made in lessening the impact of tuberculosis (TB) on human health, especially in parts of the world where Mtb is endemic. Due to the complexity of TB disease, there is still an urgent need to improve diagnosis, prevention, and treatment strategies to control global spread of disease. Active research targeting avenues to prevent infection or transmission through vaccination, to diagnose asymptomatic carriers of Mtb, and to improve antimicrobial drug treatment responses is ongoing. However, this research is hampered by a relatively poor understanding of the pathogenesis of early infection and the factors that contribute to host susceptibility, protection, and the development of active disease. There is increasing interest in the development of adjunctive therapy that will aid the host in responding to Mtb infection appropriately thereby improving the effectiveness of current and future drug treatments. In this review, we summarize what is known about the host response to Mtb infection in humans and animal models and highlight potential therapeutic targets involved in TB granuloma formation and resolution. Strategies designed to shift the balance of TB granuloma formation toward protective rather than destructive processes are discussed based on our current knowledge. These therapeutic strategies are based on the assumption that granuloma formation, although thought to prevent the spread of the tubercle bacillus within and between individuals contributes to manifestations of active TB disease in human patients when left unchecked. This effect of granuloma formation favors the spread of infection and impairs antimicrobial drug treatment. By gaining a better understanding of the mechanisms by which Mtb infection contributes to irreversible tissue damage, down regulates protective immune responses, and delays tissue healing, new treatment strategies can be rationally designed. Granuloma-targeted therapy is advantageous because it allows for the repurpose of existing drugs used to treat other communicable and non-communicable diseases as adjunctive therapies combined with existing and future anti-TB drugs. Thus, the development of adjunctive, granuloma-targeted therapy, like other host-directed therapies, may benefit from the availability of approved drugs to aid in treatment and prevention of TB. In this review, we have attempted to summarize the results of published studies in the context of new innovative approaches to host-directed therapy that need to be more thoroughly explored in pre-clinical animal studies and in human clinical trials.

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Trans‐species communication in the Mycobacterium tuberculosis‐infected macrophage

Cited by 31 publications

References 121 publications

Efferocytosis and extrusion of leukocytes determine the progression of early mycobacterial pathogenesis

Efferocytosis and extrusion of leukocytes determine the progression of early mycobacterial pathogenesis

Experimental study of tuberculosis: From animal models to complex cell systems and organoids

Host-directed therapy targeting the Mycobacterium tuberculosis granuloma: a review

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