Possible Existence of a Novel Amphipathic Immunostimulator in the Phenol‐Water Extracts of <i>Mycobacteriaceae</i>

Ikeda-Fujita, Takako; Kotani, Shozo; Tsujimoto, M; Ogawa, Tomohiko; Takahashi, Ichiro; Takada, Haruhiko; Shimauchi, Hidetoshi; Nagao, Shigeki; Kokeguchi, Susumu; Kato, Kimiko; Yano, Ikuya; Okamura, Haruki; Tamura, T.; Harada, Kazuhiro; Usami, Hatsuhiko; Yamamoto, Akihiko; Tanaka, Shigenori; Kato, Yoshiko

doi:10.1111/j.1348-0421.1987.tb03091.x

Cited by 13 publications

(6 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast, TLR2 is not required for LPS signaling, a process that is blocked by expression of dominant negative murine TLR4 (P712H) (31). These observations are consistent with reports showing that a mutation in the TLR4 gene is responsible for the LPS hyporesponsiveness of the C3H͞HeJ mouse (24,25) and that these mice are responsive to mycobacterial products (15). Recently, it has been shown that a dominant negative form of human TLR2 (lacking the C-terminal 13 aa) blocked stimulation of IL-12 and inducible nitric oxide synthase (iNOS) in macrophages by a lipoprotein derived from M. tuberculosis.…”

Section: Resultssupporting

confidence: 90%

“…Because macrophages from mice bearing a dysfunctional TLR4 secrete TNF-␣ normally in response to mycobacterial products (15), it is unlikely that TLR4 contributes to macrophage activation by mycobacteria. We hypothesized that TLR2, another toll-like receptor implicated in LPS signaling (18,19), is the toll-like receptor responsible for mycobacterial activation of macrophages.…”

Section: Resultsmentioning

confidence: 99%

“…Macrophages from C3H͞HeJ mice respond poorly to stimulation by LPS, yet they secrete proinflammatory mediators normally in response to mycobacterial products (15). Conversely, Chinese hamster ovary (CHO) fibroblasts transfected with CD14 respond to LPS (16), but fail to respond to LAM (9).…”

Section: Myd88 ͉ Mycobacterium Tuberculosis ͉ Tumor Necrosis Factor ␣mentioning

confidence: 99%

See 2 more Smart Citations

Toll-like receptor-2 mediates mycobacteria-induced proinflammatory signaling in macrophages

Underhill

Ozinsky

Smith

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

746

522

View full text Add to dashboard Cite

The recognition of mycobacterial cell wall components causes macrophages to secrete tumor necrosis factor ␣ (TNF-␣) and other cytokines that are essential for the development of a protective inflammatory response. We show that toll-like receptors are required for the induction of TNF-␣ in macrophages by Mycobacterium tuberculosis. Expression of a dominant negative form of MyD88 (a signaling component required for toll-like receptor signaling) in a mouse macrophage cell line blocks TNF-␣ production induced by M. tuberculosis. We identify toll-like receptor-2 (TLR2) as the specific toll-like receptor required for this induction by showing that expression of an inhibitory TLR2 (TLR2-P681H) blocks TNF-␣ production induced by whole M. tuberculosis. Further, we show that TLR2-dependent signaling mediates responses to mycobacterial cell wall fractions enriched for lipoarrabinomannan, mycolylarabinogalactan-peptidoglycan complex, or M. tuberculosis total lipids. Thus, although many mycobacterial cell wall fractions are identified to be inflammatory, all require TLR2 for induction of TNF-␣ in macrophages. These data suggest that TLR2 is essential for the induction of a protective immune response to mycobacteria.

show abstract

Section: Resultssupporting

confidence: 90%

Section: Resultsmentioning

confidence: 99%

Section: Myd88 ͉ Mycobacterium Tuberculosis ͉ Tumor Necrosis Factor ␣mentioning

confidence: 99%

See 1 more Smart Citation

Toll-like receptor-2 mediates mycobacteria-induced proinflammatory signaling in macrophages

Underhill

Ozinsky

Smith

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

746

522

View full text Add to dashboard Cite

show abstract

“…Less-well-characterized LAM family lipoglycans have been identified in a number of other representatives of the mycolata (12,13,19,30,42,52,53;Sutcliffe and Garton,unpublished data). It thus seems likely that the structural diversity of the LAM family has yet to be fully defined.…”

Section: Discussionmentioning

confidence: 99%

Characterization of a Truncated Lipoarabinomannan from the Actinomycete Turicella otitidis

et al. 2005

View full text Add to dashboard Cite

Lipoarabinomannan (LAM) lipoglycans have been characterized from a range of mycolic acid-containing actinomycetes and from the amycolate actinomycete Amycolatopsis sulphurea. To further understand the structural diversity of this family, we have characterized the lipoglycan of the otic commensal Turicella otitidis. T. otitidis LAM (TotLAM) has been determined to consist of a mannosyl phosphatidylinositol anchor unit carrying an (␣ 136)-linked mannan core and substituted with terminal-arabinosyl branches. Thus, TotLAM has a novel truncated LAM structure. Using the human monocytic THP-1 cell line, it was found that TotLAM exhibited only minimal ability to induce tumor necrosis factor alpha. These findings contribute further to our understanding of actinomycete LAM diversity and allow further speculation as to the correlation between LAM structure and the immunomodulatory activities of these lipoglycans.The cell envelopes of gram-positive bacteria contain structurally diverse macroamphiphilic membrane-anchored polymers that can be classified as either lipoteichoic acids or lipoglycans (11,54,56). Although considered to play important roles, the functions of these macromolecules remain unknown and it is not known if a common function underlies their structural diversity. Lipoteichoic acids predominate in the Bacillus-Streptococcus-Clostridium (Firmicutes) lineage of grampositive bacteria, whereas Mollicutes and actinomycete bacteria typically synthesize lipoglycans (54). Actinomycete lipoglycans can be classified into a number of structural archetypes (54), of which the most extensively studied are the mycobacterial lipoarabinomannans (LAM) (6,7,39). LAM-like lipoglycans have also been identified in phylogenetically close relatives of the mycobacteria, which share common cell envelope features dominated by the presence of mycolic acids (13,52,55), and three lipoglycans from this taxon (the mycolata) have been recently characterized as structurally related members of a LAM family: ReqLAM from the equine pathogen Rhodococcus equi (18), RruLAM from Rhodococcus ruber (22), and TpaLAM from Tsukamurella paurometabola (20). Moreover, an additional representative of the LAM family (AsuLAM) has been characterized from the more distantly related actinomycete Amycolatopsis sulphurea (21), which lacks mycolic acids. In each of the LAM-like lipoglycans, the carbohydrate domain consists of a linear (␣ 136) mannan backbone and an arabinan portion either consisting of few units glycosylating the mannan core or organized as an independent domain, as observed in mycobacteria.The mycolata lineage also encompasses a few species that appear to have lost the ability to synthesize mycolates, including Turicella otitidis, the type species of the monospecific genus Turicella (16, 17). T. otitidis is part of the normal flora of the ear (15, 29, 51) that may cause opportunistic infections such as acute otitis media (8,16,17,44,45,48). However, in contrast to reports that it is an exclusively otic organism, it has also been isolated in a case ...

show abstract

“…Lipoglycans apparently structurally related to LAM have been identified in representative organisms of other genera within the mycolata, including Corynebacterium matruchotii (22), Dietzia maris (23), Gordonia rubropertincta (24,25), and Rhodococcus rhodnii (26). Although these lipoglycans display components typical of LAM, considerable variation in monosaccharide composition has been found.…”

mentioning

confidence: 99%

A Novel Lipoarabinomannan from the Equine PathogenRhodococcus equi

Garton¹,

Gilleron²,

Brando³

et al. 2002

Journal of Biological Chemistry

View full text Add to dashboard Cite

Rhodococcus equi is a major cause of foal morbidity and mortality. We have investigated the presence of lipoglycan in this organism as closely related bacteria, notably Mycobacterium tuberculosis, produce lipoarabinomannans (LAM) that may play multiple roles as virulence determinants. The lipoglycan was structurally characterized by gas chromatography-mass spectrometry following permethylation, capillary electrophoresis after chemical degradation, and 1 H and 31 P and twodimensional heteronuclear nuclear magnetic resonance studies. Key structural features of the lipoglycan are a linear ␣-1,6-mannan with side chains containing one 2-linked ␣-D-Manp residue. This polysaccharidic backbone is linked to a phosphatidylinositol mannosyl anchor. In contrast to mycobacterial LAM, there are no extensive arabinan domains but single terminal ␣-D-Araf residue capping the 2-linked ␣-D-Manp. The lipoglycan binds concanavalin A and mannose-binding protein consistent with the presence of t-␣-D-Manp residues. We studied the ability of the lipoglycans to induce cytokines from equine macrophages, in comparison to whole cells of R. equi. These data revealed patterns of cytokine mRNA induction that suggest that the lipoglycan is involved in much of the early macrophage cytokine response to R. equi infection. These studies identify a novel LAM variant that may contribute to the pathogenesis of disease caused by R. equi.

show abstract

Possible Existence of a Novel Amphipathic Immunostimulator in the Phenol‐Water Extracts of Mycobacteriaceae

Abstract: The extracts having diverse

Cited by 13 publications

References 31 publications

Toll-like receptor-2 mediates mycobacteria-induced proinflammatory signaling in macrophages

Toll-like receptor-2 mediates mycobacteria-induced proinflammatory signaling in macrophages

Characterization of a Truncated Lipoarabinomannan from the Actinomycete Turicella otitidis

A Novel Lipoarabinomannan from the Equine PathogenRhodococcus equi

Contact Info

Product

Resources

About