Innate response of human endothelial cells infected with mycobacteria

Garcı́a-Pérez, Blanca Estela; Villagómez-Palatto, Daniela A.; Castañeda‐Sánchez, Jorge Ismael; Coral‐Vázquez, Ramón Mauricio; Ramírez-Sánchez, Israel; Ordóñez-Razo, Rosa María; Luna-Herrera, Julieta

doi:10.1016/j.imbio.2011.01.004

Cited by 31 publications

(25 citation statements)

References 63 publications

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“…Further confirmation was obtained following staining of the infected embryos with a probe that detects reactive oxygen species (ROS) (CellROX) (Fig 3C). At 1 dpi, ROS-labeled infected macrophages were found in WT embryos (Fig 3D), in agreement with previous reports showing that macrophages can produce ROS to control Mabs infections [25,26]. No differences in the proportion of ROS-positive macrophages containing either Mabs S or R were noticed (Fig 3D).…”

Section: Resultssupporting

confidence: 91%

Mycobacterium abscessus-Induced Granuloma Formation Is Strictly Dependent on TNF Signaling and Neutrophil Trafficking

et al. 2016

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Mycobacterium abscessus is considered the most common respiratory pathogen among the rapidly growing non-tuberculous mycobacteria. Infections with M. abscessus are increasingly found in patients with chronic lung diseases, especially cystic fibrosis, and are often refractory to antibiotic therapy. M. abscessus has two morphotypes with distinct effects on host cells and biological responses. The smooth (S) variant is recognized as the initial airway colonizer while the rough (R) is known to be a potent inflammatory inducer associated with invasive disease, but the underlying immunopathological mechanisms of the infection remain unsolved. We conducted a comparative stepwise dissection of the inflammatory response in S and R pathogenesis by monitoring infected transparent zebrafish embryos. Loss of TNFR1 function resulted in increased mortality with both variants, and was associated with unrestricted intramacrophage bacterial growth and decreased bactericidal activity. The use of transgenic zebrafish lines harboring fluorescent macrophages and neutrophils revealed that neutrophils, like macrophages, interact with M. abscessus at the initial infection sites. Impaired TNF signaling disrupted the IL8-dependent neutrophil mobilization, and the defect in neutrophil trafficking led to the formation of aberrant granulomas, extensive mycobacterial cording, unrestricted bacterial growth and subsequent larval death. Our findings emphasize the central role of neutrophils for the establishment and maintenance of the protective M. abscessus granulomas. These results also suggest that the TNF/IL8 inflammatory axis is necessary for protective immunity against M. abscessus and may be of clinical relevance to explain why immunosuppressive TNF therapy leads to the exacerbation of M. abscessus infections.

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Section: Resultssupporting

confidence: 91%

Mycobacterium abscessus-Induced Granuloma Formation Is Strictly Dependent on TNF Signaling and Neutrophil Trafficking

et al. 2016

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“…Intravacuolar mycobacteria destruction was clearly observed, and partial destruction of the bacterial cell wall was evident (Figure 5b). The results from the analysis of mycobacterial intracellular elimination, membrane protrusion formation, and cytoskeleton rearrangements during bacterial uptake resemble those observed in the infection of epithelial and endothelial cells by M. smegmatis [19,35], although M. smegmatis induced significantly fewer changes in endothelial cells. To our knowledge, there are no other reports of B cell infection by M. smegmatis ; therefore, this study is the first description of this subject.…”

Section: Discussionsupporting

confidence: 53%

“…In our study, B lymphoblast cells of the Raji cell line (Burkitt’s lymphoma) were infected with two Mycobacterium species and with S. typhimurium , and the resultant cellular membrane changes and cytoskeletal reorganisation events were analysed. We previously reported that macropinocytosis is the mechanism responsible for the internalisation of mycobacteria into the lung epithelial A549 cell line [18,19] and into endothelial cells [35]. Therefore, considering that B lymphocytes have been recognised as classical non-phagocytic cells [29], we sought to establish whether mycobacteria were able to induce macropinocytic internalisation in B cells.…”

Section: Discussionmentioning

confidence: 99%

“…M. tuberculosis has previously demonstrated the capability to invade several cell types, including epithelial [18,38], fibroblast [39], and endothelial cells [35,40]. The cellular membrane protrusions formed during M. tuberculosis internalisation have been described in some of these cells [18,35,40]. In B cells, membrane protrusions were also observed during M. tuberculosis uptake.…”

Section: Discussionmentioning

confidence: 99%

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Macropinocytosis is responsible for the uptake of pathogenic and non-pathogenic mycobacteria by B lymphocytes (Raji cells)

et al. 2012

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BackgroundThe classical roles of B cells include the production of antibodies and cytokines and the generation of immunological memory, these being key factors in the adaptive immune response. However, their role in innate immunity is currently being recognised. Traditionally, B cells have been considered non-phagocytic cells; therefore, the uptake of bacteria by B cells is not extensively documented. In this study, we analysed some of the features of non-specific bacterial uptake by B lymphocytes from the Raji cell line. In our model, B cells were infected with Mycobacterium tuberculosis (MTB), Mycobacterium smegmatis (MSM), and Salmonella typhimurium (ST).ResultsOur observations revealed that the Raji B cells were readily infected by the three bacteria that were studied. All of the infections induced changes in the cellular membrane during bacterial internalisation. M. smegmatis and S. typhimurium were able to induce important membrane changes that were characterised by abundant filopodia and lamellipodia formation. These membrane changes were driven by actin cytoskeletal rearrangements. The intracellular growth of these bacteria was also controlled by B cells. M. tuberculosis infection also induced actin rearrangement-driven membrane changes; however, the B cells were not able to control this infection. The phorbol 12-myristate 13-acetate (PMA) treatment of B cells induced filopodia and lamellipodia formation, the production of spacious vacuoles (macropinosomes), and the fluid-phase uptake that is characteristic of macropinocytosis. S. typhimurium infection induced the highest fluid-phase uptake, although both mycobacteria also induced fluid uptake. A macropinocytosis inhibitor such as amiloride was used and abolished the bacterial uptake and the fluid-phase uptake that is triggered during the bacterial infection.ConclusionsRaji B cells can internalise S. typhimurium and mycobacteria through an active process, such as macropinocytosis, although the resolution of the infection depends on factors that are inherent in the virulence of each pathogen.

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“…In the case of M. abscessus , both superoxide anion release and neutrophil killing is limited, and suggests that M. abscessus possesses mechanisms for avoiding reactive oxygen species accumulation and/or superoxide-dependent death, such as expression of superoxide dismutase and catalase, as seen with M. tuberculosis [44]. In endothelial cells, M. abscessus produced relatively little reactive oxygen species, yet was a relatively strong inducer of reactive nitrogen species compared to other mycobacteria [15]. Recently, oxidative stress in macrophages was shown to be important in supporting the growth of M. abscessus rather than as a killing mechanism [43].…”

Section: Discussionmentioning

confidence: 99%

Mycobacterium abscessus Induces a Limited Pattern of Neutrophil Activation That Promotes Pathogen Survival

et al. 2013

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Mycobacterium abscessus is a rapidly growing mycobacterium increasingly detected in the neutrophil-rich environment of inflamed tissues, including the cystic fibrosis airway. Studies of the immune reaction to M. abscessus have focused primarily on macrophages and epithelial cells, but little is known regarding the neutrophil response despite the predominantly neutrophillic inflammation typical of these infections. In the current study, human neutrophils released less superoxide anion in response to M. abscessus than to Staphylococcus aureus, a pathogen that shares common sites of infection. Exposure to M. abscessus induced neutrophil-specific chemokine and proinflammatory cytokine genes. Although secretion of these protein products was confirmed, the quantity of cytokines released, and both the number and level of gene induction, was reduced compared to S. aureus. Neutrophils mediated killing of M. abscessus, but phagocytosis was reduced when compared to S. aureus, and extracellular DNA was detected in response to both bacteria, consistent with extracellular trap formation. In addition, M. abscessus did not alter cell death compared to unstimulated cells, while S. aureus enhanced necrosis and inhibited apoptosis. However, neutrophils augment M. abscessus biofilm formation. The response of neutrophils to M. abscessus suggests that the mycobacterium exploits neutrophil-rich settings to promote its survival and that the overall neutrophil response was reduced compared to S. aureus. These studies add to our understanding of M. abscessus virulence and suggest potential targets of therapy.

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Innate response of human endothelial cells infected with mycobacteria

Cited by 31 publications

References 63 publications

Mycobacterium abscessus-Induced Granuloma Formation Is Strictly Dependent on TNF Signaling and Neutrophil Trafficking

Mycobacterium abscessus-Induced Granuloma Formation Is Strictly Dependent on TNF Signaling and Neutrophil Trafficking

Macropinocytosis is responsible for the uptake of pathogenic and non-pathogenic mycobacteria by B lymphocytes (Raji cells)

Mycobacterium abscessus Induces a Limited Pattern of Neutrophil Activation That Promotes Pathogen Survival

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