Mouse Cachexia Induced by Trehalose Dimycolate from Nocardia asteroides

Silva, Célio Lopes; Tincani, Izaira; Filho, Sebastião L. Brandão; Faccioli, Lúcia Helena

doi:10.1099/00221287-134-6-1629

Cited by 8 publications

(19 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The amino acid side chains consist of diamidated L-alanine-D-ct-glutamine-meso-DAP tripeptides and L-alanine-D-ct-glutaminemeso-DAP-D-alanine tetrapeptides (29,688 333-336, 412, 469, 614). This trehalose-6,6'-dimycolate (cord factor) has specific biologic activity; it is toxic, it inhibits calcium-dependent membrane fusion, it inhibits phagosome-lysosome fusion in macrophages, and it appears to be associated with nocardial virulence (336,615,629,630,661,729). Furthermore, there are specific additional fatty acids and mycolic acids firmly linked to the cell wall.…”

Section: Mechanisms Of Nocardl4 Pathogenesismentioning

confidence: 99%

“…Microgram amounts of cord factor emulsified in mineral oil are lethal for mice (279,336,615,617). Furthermore, cord factors alter leukocyte migration, have antitumor activity, serve as immunomodulators, are toxic to mitochondria, and induce foreign body granulomas (i.e., are granulomogenic) (279,355).…”

Section: Role Of Mycolic Acids In Nocardia-host Interactionsmentioning

confidence: 99%

“…(24,86,120,226,227,279,333,335,336,491,614,615,630,729). Most of these are composed of large hydroxylated fatty acids (mycolic acids as described above) esterified to the disaccharide trehalose to form a trehalose glycolipid (279).…”

Section: Role Of Mycolic Acids In Nocardia-host Interactionsmentioning

confidence: 99%

See 2 more Smart Citations

Nocardia species: host-parasite relationships

1994

View full text Add to dashboard Cite

The nocardiae are bacteria belonging to the aerobic actinomycetes. They are an important part of the normal soil microflora worldwide. The type species, Nocardia asteroides, and N. brasiliensis, N. farcinica, N. otitidiscaviarum, N. nova, and N. transvalensis cause a variety of diseases in both normal and immunocompromised humans and animals. The mechanisms of pathogenesis are complex, not fully understood, and include the capacity to evade or neutralize the myriad microbicidal activities of the host. The relative virulence of N. asteroides correlates with the ability to inhibit phagosome-lysosome fusion in phagocytes; to neutralize phagosomal acidification; to detoxify the microbicidal products of oxidative metabolism; to modify phagocyte function; to grow within phagocytic cells; and to attach to, penetrate, and grow within host cells. Both activated macrophages and immunologically specific T lymphocytes constitute the major mechanisms for host resistance to nocardial infection, whereas B lymphocytes and humoral immunity do not appear to be as important in protecting the host. Thus, the nocardiae are facultative intracellular pathogens that can persist within the host, probably in a cryptic form (L-form), for life. Silent invasion of brain cells by some Nocardia strains can induce neurodegeneration in experimental animals; however, the role of nocardiae in neurodegenerative diseases in humans needs to be investigated.

show abstract

Section: Mechanisms Of Nocardl4 Pathogenesismentioning

confidence: 99%

Section: Role Of Mycolic Acids In Nocardia-host Interactionsmentioning

confidence: 99%

See 1 more Smart Citation

Nocardia species: host-parasite relationships

1994

View full text Add to dashboard Cite

show abstract

“…In addition to the diethyl ethersoluble lipids, other wall-associated lipids of N. asteroides are known to induce inflammatory responses when systemically administered. The most notable of these compounds is 6,6=-trehalose dimycolate, or TDM, which induces a strong and deadly cachectic state when systemically administered to mice (42). When administered subdermally, TDM can also induce a strong, local inflammatory response that mimics important histopathological aspects of the disease caused by N. asteroides, including the induction of granuloma formation (19).…”

mentioning

confidence: 99%

Nocardia brasiliensis Cell Wall Lipids Modulate Macrophage and Dendritic Responses That Favor Development of Experimental Actinomycetoma in BALB/c Mice

et al. 2012

View full text Add to dashboard Cite

Nocardia brasiliensis is a Gram-positive facultative intracellular bacterium frequently isolated from human actinomycetoma. However, the pathogenesis of this infection remains unknown. Here, we used a model of bacterial delipidation with benzine to investigate the role of N. brasiliensis cell wall-associated lipids in experimental actinomycetoma. Delipidation of N. brasiliensis with benzine resulted in complete abolition of actinomycetoma without affecting bacterial viability. Chemical analyses revealed that trehalose dimycolate and an unidentified hydrophobic compound were the principal compounds extracted from N. brasiliensis with benzine. By electron microscopy, the extracted lipids were found to be located in the outermost membrane layer of the N. brasiliensis cell wall. They also appeared to confer acid-fastness. In vitro, the extractable lipids from the N. brasiliensis cell wall induced the production of the proinflammatory cytokines interleukin-1␤ (IL-1␤), IL-6, and CCL-2 in macrophages. The N. brasiliensis cell wall extractable lipids inhibited important macrophage microbicidal effects, such as tumor necrosis factor alpha (TNF-␣) and nitric oxide (NO) production, phagocytosis, bacterial killing, and major histocompatibility complex class II (MHC-II) expression in response to gamma interferon (IFN-␥). In dendritic cells (DCs), N. brasiliensis cell wall-associated extractable lipids suppressed MHC-II, CD80, and CD40 expression while inducing tumor growth factor ␤ (TGF-␤) production. Immunization with delipidated N. brasiliensis induced partial protection preventing actinomycetoma. These findings suggest that N. brasiliensis cell wall-associated lipids are important for actinomycetoma development by inducing inflammation and modulating the responses of macrophages and DCs to N. brasiliensis.

show abstract

“…Therefore, we have studied the induction of IFN and TNF in I CR mice primed with GaGM prepared in liposomes and elicited by LPS. Furthermore, since Silva et al recently reported that intraperitoneal administration of cord factor can induce TNF production without further eliciting by LPS (21,22), we have also examined this possibility by priming only with GaGM prepared in liposomes. The results showed in our system that both the priming with GaGM and eliciting with LPS are essential for the induction of TNF and we could not detect an appreciable level of TNF without LPS.…”

mentioning

confidence: 99%