Bacterial Complement Escape

Jongerius, Ilse; Ram, Sanjay; Rooijakkers, Suzan H.M.

doi:10.1007/978-1-4419-1601-3_3

Cited by 11 publications

(5 citation statements)

References 151 publications

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“…In many bacterial pathogens, cell envelope stress responses play a multifaceted role. They provide protection against damage caused by components of the immune system, such as complement and antimicrobial peptides that target the cell envelope [3-5]. They regulate the expression of chaperones required for proper assembly of cell envelope-associated structures, including outer membrane porins, pili, and fimbrae [3,6,7].…”

Section: Introductionmentioning

confidence: 99%

sigE facilitates the adaptation of Bordetella bronchiseptica to stress conditions and lethal infection in immunocompromised mice

et al. 2012

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BackgroundThe cell envelope of a bacterial pathogen can be damaged by harsh conditions in the environment outside a host and by immune factors during infection. Cell envelope stress responses preserve the integrity of this essential compartment and are often required for virulence. Bordetella species are important respiratory pathogens that possess a large number of putative transcription factors. However, no cell envelope stress responses have been described in these species. Among the putative Bordetella transcription factors are a number of genes belonging to the extracytoplasmic function (ECF) group of alternative sigma factors, some of which are known to mediate cell envelope stress responses in other bacteria. Here we investigate the role of one such gene, sigE, in stress survival and pathogenesis of Bordetella bronchiseptica.ResultsWe demonstrate that sigE encodes a functional sigma factor that mediates a cell envelope stress response. Mutants of B. bronchiseptica strain RB50 lacking sigE are more sensitive to high temperature, ethanol, and perturbation of the envelope by SDS-EDTA and certain β-lactam antibiotics. Using a series of immunocompromised mice deficient in different components of the innate and adaptive immune responses, we show that SigE plays an important role in evading the innate immune response during lethal infections of mice lacking B cells and T cells. SigE is not required, however, for colonization of the respiratory tract of immunocompetent mice. The sigE mutant is more efficiently phagocytosed and killed by peripheral blood polymorphonuclear leukocytes (PMNs) than RB50, and exhibits decreased cytotoxicity toward macrophages. These altered interactions with phagocytes could contribute to the defects observed during lethal infection.ConclusionsMuch of the work on transcriptional regulation during infection in B. bronchiseptica has focused on the BvgAS two-component system. This study reveals that the SigE regulon also mediates a discrete subset of functions associated with virulence. SigE is the first cell envelope stress-sensing system to be described in the bordetellae. In addition to its role during lethal infection of mice deficient in adaptive immunity, our results indicate that SigE is likely to be important for survival in the face of stresses encountered in the environment between hosts.

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Section: Introductionmentioning

confidence: 99%

sigE facilitates the adaptation of Bordetella bronchiseptica to stress conditions and lethal infection in immunocompromised mice

et al. 2012

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“…Activation of the CP and lectin pathway results in cleavage of C4; deposited C4b can bind to C2, and cleavage of the latter generates C4b,2a, which functions as a C3 convertase. Cleavage of C3 by convertases is a critical event in complement activation, because it leads to release of the anaphylatoxin C3a and deposition of C3b on the bacterial surface (5). Strict regulation of the complement system is necessary to avoid inappropriate activation and host cell damage.…”

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confidence: 99%

Neisseria meningitidis NalP cleaves human complement C3, facilitating degradation of C3b and survival in human serum

Tordello

Vacca

Ram

et al. 2013

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

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The complement system is a crucial component of the innate immune response against invading bacterial pathogens. The human pathogen Neisseria meningitidis (Nm) is known to possess several mechanisms to evade the complement system, including binding to complement inhibitors. In this study, we describe an additional mechanism used by Nm to evade the complement system and survive in human blood. Using an isogenic NalP deletion mutant and NalP complementing strains, we show that the autotransporter protease NalP cleaves C3, the central component of the complement cascade. The cleavage occurs 4 aa upstream from the natural C3 cleavage site and produces shorter C3a-like and longer C3b-like fragments. The C3b-like fragment is degraded in the presence of the complement regulators (factors H and I), and this degradation results in lower deposition of C3b on the bacterial surface. We conclude that NalP is an important factor to increase the survival of Nm in human serum.serum resistance | immune evasion

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“…Bacteria and viruses are known to interfere with innate immune responses by producing proteases that degrade host defense factors, 16 secreting exact replicates of human cytokines that suppress immune response, 17 cleaving or evading complement activation, 18 impeding phagocyte recruitment, 19 interfering with reactive oxygen species, 20 escaping neutrophil extracellular traps, 21 and generating pore-forming cytolysins, 22 among other mechanisms.…”

Section: Defense Against Innate Immunitymentioning

confidence: 99%

Immune camouflage: Relevance to vaccines and human immunology

Groot

Moise

et al. 2014

Human Vaccines & Immunotherapeutics

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High strain sequence variability, interference with innate immune mechanisms, and epitope deletion are all examples of strategies that pathogens have evolved to subvert host defenses. To this list we would add another strategy: immune camouflage. Pathogens whose epitope sequences are cross-conserved with multiple human proteins at the TCR-facing residues may be exploiting “ignorance and tolerance," which are mechanisms by which mature T cells avoid immune responses to self-antigens. By adopting amino acid configurations that may be recognized by autologous regulatory T cells, pathogens may be actively suppressing protective immunity. Using the new JanusMatrix TCR-homology-mapping tool, we have identified several such ‘camouflaged’ tolerizing epitopes that are present in the viral genomes of pathogens such as emerging H7N9 influenza. Thus in addition to the overall low number of T helper epitopes that is present in H7 hemaglutinin (as described previously, see http://dx.doi.org/10.4161/hv.24939), the presence of such tolerizing epitopes in H7N9 could explain why, in recent vaccine trials, whole H7N9-HA was poorly immunogenic and associated with low seroconversion rates (see http://dx.doi.org/10.4161/hv.28135). In this commentary, we provide an overview of the immunoinformatics process leading to the discovery of tolerizing epitopes in pathogen genomic sequences, provide a brief summary of laboratory data that validates the discovery, and point the way forward. Removal of viral, bacterial and parasite tolerizing epitopes may permit researchers to develop more effective vaccines and immunotherapeutics in the future.

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Bacterial Complement Escape

Cited by 11 publications

References 151 publications

sigE facilitates the adaptation of Bordetella bronchiseptica to stress conditions and lethal infection in immunocompromised mice

sigE facilitates the adaptation of Bordetella bronchiseptica to stress conditions and lethal infection in immunocompromised mice

Neisseria meningitidis NalP cleaves human complement C3, facilitating degradation of C3b and survival in human serum

Immune camouflage: Relevance to vaccines and human immunology

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