Failure of lipopolysaccharide (LPS) to activate the alternative pathway of complement

Hoffmann, Edward M.; Houle, J.J.

doi:10.1016/0165-2427(83)90032-6

Cited by 34 publications

(19 citation statements)

References 12 publications

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“…The lectin pathway with MBP might be involved in the high anti-complement activity of B. melitensis LPS. Brucella LPS is reported to fail in the activation of the alternative pathway of complement (10,17). It might be reasonable because the lectin pathway occurs on the O-specific polysaccharide moiety and eliminates the activation of the alternative pathway occurring on the same polysaccharide moiety.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Biological Activities of Brucella melitensis Lipopolysaccharide

Tumurkhuu

Koide

Takahashi

et al. 2006

Microbiology and Immunology

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Brucella are Gram-negative intracellular pathogens which survive within a variety of cells including macrophages and maintain a long-lasting interaction with the host cells (11,15). The infection leads to acute and chronic inflammation related to the brisk interaction of Brucella-derived products, such as lipopolysaccharide (LPS) with the host cells. In fact, Brucella LPS is reported to act as a virulence factor of the infection (19,22). Most wild-type Brucella have smooth type LPS (S-LPS) consisting of three domains: lipid A, core oligosaccharide, and O-specific polysaccharide (21). Among Brucella LPSs, LPS from B. abortus has been extensively characterized (reviewed in 22). The lipid A moiety of B. abortus LPS has a fatty acid composition quite distinct from that of enterobacterial LPS. Specifically, the lipid A moiety of B. abortus LPS possesses a diaminoglucose backbone, and the acyl groups are longer (C18-19, C28) and are only linked to the core by amide bounds (22,30). Further, the O antigen of Brucella LPS is a homopolymer of perosamine (4,6-dideoxy-4-formamido-d-mannopyranosyl) (3, 27, 37). The biological activities such as cytokine production and lethality of S-LPS and rough types of LPS (R-LPS) from various Brucella strains are reported to be lower than those of enterobacterial LPS (4,14,25,29). The lower endotoxicity seems to be responsible for the unique lipid A structure of Brucella LPS. Thus, LPS from B. abortus has been studied as a representative of Brucella. On the other hand, B. melitensis is another main pathogenic species for humans worldwide (6). However, the chemical structure of B. melitensis LPS is not as fully clarified as that of B. abortus LPS. Further, there is no systemic study on the biological activities of B. melitensis LPS, although some biological activities are reported (7,(23)(24)(25). In the present study, we compared the biological activities of B. melitensis LPS with those of enterobacterial LPS in order to characterize the biological activities of B. melitensis LPS. Materials and Methods LPS.Crude LPS preparation was extracted from B. melitensis 16M (biotype 1). Briefly, washed cells of B. melitensis were autoclaved at 120 C for 30 min. After removal of the cell debris by centrifugation, the crude LPS fraction was precipitated with methanol, dialyzed and freeze-dried. For further purification, the LPS preparation was digested with DNase I, RNase and pro- Characterization of Biological Activities of

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Section: Discussionmentioning

confidence: 99%

Characterization of Biological Activities of Brucella melitensis Lipopolysaccharide

Tumurkhuu

Koide

Takahashi

et al. 2006

Microbiology and Immunology

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“…Early in infection, resistance to complement (29) and cationic peptide-mediated attacks (32), as well as protection against host recognition of PAMPs (31), enhance Brucella survival before the bacterium reaches its intracellular niche, the macrophage. Immediately after entry into macrophages, Brucella resides in an acidified compartment that fuses with components of the early endosomal pathway (7).…”

Section: Discussionmentioning

confidence: 99%

Brucella abortusInhibits Major Histocompatibility Complex Class II Expression and Antigen Processing through Interleukin-6 Secretion via Toll-Like Receptor 2

et al. 2008

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The strategies that allow Brucella abortus to survive inside macrophages for prolonged periods and to avoid the immunological surveillance of major histocompatibility complex class II (MHC- Infection with Brucella abortus has been shown to potently activate both the innate and adaptive arms of the immune system, leading to a proinflammatory response that favors the differentiation of T-cell responses toward a T-helper 1 (Th1) profile (15,(55)(56)(57). Despite this immune response, B. abortus can persist for years inside macrophages, evading host immune responses.IIMacrophages are an early barrier for defense against Brucella. They phagocytose and degrade invading microorganisms, participating actively in innate immunity. Additionally, by processing microorganisms within intracellular compartments, they present peptides in the context of the major histocompatibility complex (MHC) to T lymphocytes, promoting the adaptive immune response. Gamma interferon (IFN-␥) has a critical role in protective immunity against Brucella. This cytokine enhances both the microbicidal and antigen-presenting functions of macrophages (12,18,19,48). Thus, the virulence of B. abortus relies on the ability of this organism to survive and replicate within vacuolar phagocytic compartments of macrophages (26,30), and the macrophage-Brucella interaction is critical for the establishment of chronic Brucella infections.

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“…Because the major surface component of Brucella is an LPS, the interaction between Brucella and complement components will be mediated by this molecule. In general, smooth strains of B. abortus are more resistant than OPS-deficient rough strains to serum bactericidal activity (37) because B. abortus LPS obtained from smooth strains does not activate the alternative pathway (72). Thus, the action of the classical pathway mediated by IgM and low concentrations of IgG has been considered to be the dominant bactericidal action of serum against B. abortus mediated in the early stage of infection.…”

Section: Brucella Immunity Innate Immunitymentioning

confidence: 99%

Molecular Host-Pathogen Interaction in Brucellosis: Current Understanding and Future Approaches to Vaccine Development for Mice and Humans

2003

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Brucellosis caused by Brucella spp. is a major zoonotic disease. Control of brucellosis in agricultural animals is a prerequisite for the prevention of this disease in human beings. Recently, Brucella melitensis was declared by the Centers for Disease Control and Prevention to be one of three major bioterrorist agents due to the expense required for the treatment of human brucellosis patients. Also, the economic agricultural loss due to bovine brucellosis emphasizes the financial impact of brucellosis in society. Thus, vaccination might efficiently solve this disease. Currently, B. abortus RB51 and B. melitensis REV.1 are used to immunize cattle and to immunize goats and sheep, respectively, in many countries. However, these genetically undefined strains still induce abortion and persistent infection, raising questions of safety and efficiency. In fact, the REV.1 vaccine is quite virulent and apparently unstable, creating the need for improved vaccines for B. melitensis. In addition, Brucella spp. may or may not provide cross-protection against infection by heterologous Brucella species, hampering the acceleration of vaccine development. This review provides our current understanding of Brucella pathogenesis and host immunity for the development of genetically defined efficient vaccine strains. Additionally, conditions required for an effective Brucella vaccine strain as well as the future research direction needed to investigate Brucella pathogenesis and host immunity are postulated

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Failure of lipopolysaccharide (LPS) to activate the alternative pathway of complement

Cited by 34 publications

References 12 publications

Characterization of Biological Activities of Brucella melitensis Lipopolysaccharide

Characterization of Biological Activities of Brucella melitensis Lipopolysaccharide

Brucella abortusInhibits Major Histocompatibility Complex Class II Expression and Antigen Processing through Interleukin-6 Secretion via Toll-Like Receptor 2

Molecular Host-Pathogen Interaction in Brucellosis: Current Understanding and Future Approaches to Vaccine Development for Mice and Humans

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