scholarly journals Resistance of Capnocytophaga canimorsus to Killing by Human Complement and Polymorphonuclear Leukocytes

2009 ◽  
Vol 77 (6) ◽  
pp. 2262-2271 ◽  
Author(s):  
Hwain Shin ◽  
Manuela Mally ◽  
Salome Meyer ◽  
Chantal Fiechter ◽  
Cécile Paroz ◽  
...  
Keyword(s):  
Type Iii Secretion ◽  
Polymorphonuclear Leukocytes ◽  
Capsular Polysaccharide ◽  
Membrane Attack Complex ◽  
Innate Immune ◽  
Classical Pathway ◽  
Wild Type ◽  
Capnocytophaga Canimorsus ◽  
Oral Flora ◽  
Human Polymorphonuclear Leukocytes

ABSTRACT Capnocytophaga canimorsus is a bacterium of the canine oral flora known since 1976 to cause rare but severe septicemia and peripheral gangrene in patients that have been in contact with a dog. It was recently shown that these bacteria do not elicit an inflammatory response (H. Shin, M. Mally, M. Kuhn, C. Paroz, and G. R. Cornelis, J. Infect. Dis. 195:375-386, 2007). Here, we analyze their sensitivity to the innate immune system. Bacteria from the archetype strain Cc5 were highly resistant to killing by complement. There was little membrane attack complex (MAC) deposition in spite of C3b deposition. Cc5 bacteria were as resistant to phagocytosis by human polymorphonuclear leukocytes (PMNs) as Yersinia enterocolitica MRS40, endowed with an antiphagocytic type III secretion system. We isolated Y1C12, a transposon mutant that is hypersensitive to killing by complement via the antibody-dependent classical pathway. The mutation inactivated a putative glycosyltransferase gene, suggesting that the Y1C12 mutant was affected at the level of a capsular polysaccharide or lipopolysaccharide (LPS) structure. Cc5 appeared to have several polysaccharidic structures, one being altered in Y1C12. The structure missing in Y1C12 could be purified by classical LPS purification procedures and labeled by tritiated palmitate, indicating that it is more likely to be an LPS structure than a capsule. Y1C12 bacteria were also more sensitive to phagocytosis by PMNs than wild-type bacteria. In conclusion, a polysaccharide structure, likely an LPS, protects C. canimorsus from deposition of the complement MAC and from efficient phagocytosis by PMNs.

scholarly journals Role of Yops and Adhesins in Resistance of Yersinia enterocolitica to Phagocytosis

2002 ◽  
Vol 70 (8) ◽  
pp. 4165-4176 ◽  
Author(s):  
Nadine Grosdent ◽  
Isabelle Maridonneau-Parini ◽  
Marie-Paule Sory ◽  
Guy R. Cornelis
Keyword(s):  
Yersinia Enterocolitica ◽  
Type Iii Secretion ◽  
Polymorphonuclear Leukocytes ◽  
Target Cells ◽  
Virulence Determinants ◽  
Wild Type ◽  
Mouse Macrophages ◽  
J774 Cells ◽  
Human Polymorphonuclear Leukocytes

ABSTRACT Yersinia enterocolitica is a pathogen endowed with two adhesins, Inv and YadA, and with the Ysc type III secretion system, which allows extracellular adherent bacteria to inject Yop effectors into the cytosol of animal target cells. We tested the influence of all of these virulence determinants on opsonic and nonopsonic phagocytosis by PU5-1.8 and J774 mouse macrophages, as well as by human polymorphonuclear leukocytes (PMNs). The adhesins contributed to phagocytosis in the absence of opsonins but not in the presence of opsonins. In agreement with previous results, YadA counteracted opsonization. In every instance, the Ysc-Yop system conferred a significant level of resistance to phagocytosis. Nonopsonized single-mutant bacteria lacking either YopE, -H, -T, or -O were phagocytosed significantly more by J774 cells and by PMNs. Opsonized bacteria were phagocytosed more than nonopsonized bacteria, and mutant bacteria lacking either YopH, -T, or -O were phagocytosed significantly more by J774 cells and by PMNs than were wild-type (WT) bacteria. Opsonized mutants lacking only YopE were phagocytosed significantly more than were WT bacteria by PMNs but not by J774 cells. Thus, YopH, -T, and -O were involved in all of the phagocytic processes studied here but YopE did not play a clear role in guarding against opsonic phagocytosis by J774. Mutants lacking YopP and YopM were, in every instance, as resistant as WT bacteria. Overexpression of YopE, -H, -T, or -O alone did not confer resistance to phagocytosis, although it affected the cytoskeleton. These results show that YopH, YopT, YopO, and, in some instances, YopE act synergistically to increase the resistance of Y. enterocolitica to phagocytosis by macrophages and PMNs.

scholarly journals Basis for the Failure of Francisella tularensis Lipopolysaccharide To Prime Human Polymorphonuclear Leukocytes

2006 ◽  
Vol 74 (6) ◽  
pp. 3277-3284 ◽  
Author(s):  
Jason H. Barker ◽  
Jerrold Weiss ◽  
Michael A. Apicella ◽  
William M. Nauseef
Keyword(s):  
Francisella Tularensis ◽  
Innate Immune System ◽  
Polymorphonuclear Leukocytes ◽  
Innate Immune ◽  
Mononuclear Leukocytes ◽  
Live Vaccine Strain ◽  
Gram Negative ◽  
Human Pmns ◽  
Human Polymorphonuclear Leukocytes ◽  
Lps Binding

ABSTRACT Francisella tularensis is the intracellular gram-negative coccobacillus that causes tularemia, and its virulence and infectiousness make it a potential agent of bioterrorism. Previous studies using mononuclear leukocytes have shown that the lipopolysaccharide (LPS) of F. tularensis is neither a typical proinflammatory endotoxin nor an endotoxin antagonist. This inertness suggests that F. tularensis LPS does not bind host LPS-sensing molecules such as LPS-binding protein (LBP). Using priming of the polymorphonuclear leukocyte (PMN) oxidase as a measure of endotoxicity, we found that F. tularensis live vaccine strain LPS did not behave like either a classic endotoxin or an endotoxin antagonist in human PMNs, even when the concentration of LBP was limiting. Furthermore, F. tularensis LPS did not compete with a radiolabeled lipooligosaccharide from Neisseria meningitidis for binding to LBP or to the closely related PMN granule protein, bactericidal/permeability-increasing protein. Our results suggest that the inertness of F. tularensis LPS and the resistance of F. tularensis to oxygen-independent PMN killing may result from the inability of F. tularensis LPS to be recognized by these important LPS-sensing molecules of the innate immune system.

scholarly journals Role of Yersinia pestis Toxin Complex Family Proteins in Resistance to Phagocytosis by Polymorphonuclear Leukocytes

2013 ◽  
Vol 81 (11) ◽  
pp. 4041-4052 ◽  
Author(s):  
Justin L. Spinner ◽  
Aaron B. Carmody ◽  
Clayton O. Jarrett ◽  
B. Joseph Hinnebusch
Keyword(s):  
Yersinia Pestis ◽  
Type Iii Secretion ◽  
Polymorphonuclear Leukocytes ◽  
Innate Immune ◽  
Content Type ◽  
Insecticidal Toxins ◽  
Toxin Complex ◽  
Human Pmns

ABSTRACTYersinia pestiscarries homologues of the toxin complex (Tc) family proteins, which were first identified in other Gram-negative bacteria as having potent insecticidal activity. TheY. pestisTc proteins are neither toxic to fleas nor essential for survival of the bacterium in the flea, even thoughtcgene expression is highly upregulated and much more of the Tc proteins YitA and YipA are produced in the flea than whenY. pestisis grownin vitro. We show that Tc+and Tc−Y. pestisstrains are transmitted equivalently from coinfected fleas, further demonstrating that the Tc proteins have no discernible role, either positive or negative, in transmission by the flea vector. Tc proteins did, however, conferY. pestiswith increased resistance to killing by polymorphonuclear leukocytes (PMNs). Resistance to killing was not the result of decreased PMN viability or increased intracellular survival but instead correlated with a Tc protein-dependent resistance to phagocytosis that was independent of the type III secretion system (T3SS). Correspondingly, we did not detect T3SS-dependent secretion of the native Tc proteins YitA and YipA or the translocation of YitA– or YipA–β-lactamase fusion proteins into CHO-K1 (CHO) cells or human PMNs. Thus, although highly produced byY. pestiswithin the flea and related to insecticidal toxins, the Tc proteins do not affect interaction with the flea or transmission. Rather, theY. pestisTc proteins inhibit phagocytosis by mouse PMNs, independent of the T3SS, and may be important for subverting the mammalian innate immune response immediately following transmission from the flea.

scholarly journals Identification of Virulent Capnocytophaga canimorsus Isolates by Capsular Typing

2017 ◽  
Vol 55 (6) ◽  
pp. 1902-1914 ◽  
Author(s):  
Estelle Hess ◽  
Francesco Renzi ◽  
Dunia Koudad ◽  
Mélanie Dol ◽  
Guy R. Cornelis
Keyword(s):  
Innate Immune System ◽  
Capsular Polysaccharide ◽  
Innate Immune ◽  
Capnocytophaga Canimorsus ◽  
Typing Method ◽  
Content Type ◽  
Severe Infections ◽  
Geographical Bias ◽  
Human Infections ◽  
Capsular Typing

ABSTRACTCapnocytophaga canimorsusis a dog oral commensal that causes rare but severe infections in humans.C. canimorsuswas recently shown to be endowed with a capsular polysaccharide implicated in resistance to the innate immune system of the host. Here, we developed the firstC. canimorsuscapsular serotyping scheme. We describe nine different serovars (A to I), and this serotyping scheme allowed typing of 25/25 isolates from human infections but only 18/52 isolates from dog mouths, indicating that the repertoire of capsules in the species is vast. However, while only three serovars (A, B, and C) covered 88% of the human isolates tested (22/25), they covered only 7.7% of the dog isolates (4/52). Serovars A, B, and C were found 22.9-, 14.6-, and 4.2-fold more often, respectively, among human isolates than among dog isolates, with no geographical bias, implying that isolates endowed with these three capsular types are more virulent for humans than other isolates. Capsular serotyping would thus allow identification of virulent isolates in dogs, which could contribute to the prevention of these infections. To this end, we developed a PCR typing method based on the amplification of specific capsular genes.

scholarly journals Role of Serotype-Specific Polysaccharide in the Resistance of Streptococcus mutans to Phagocytosis by Human Polymorphonuclear Leukocytes

2000 ◽  
Vol 68 (2) ◽  
pp. 644-650 ◽  
Author(s):  
Hiromasa Tsuda ◽  
Yoshihisa Yamashita ◽  
Kuniaki Toyoshima ◽  
Noboru Yamaguchi ◽  
Takahiko Oho ◽  
...  
Keyword(s):  
Cell Surface ◽  
Streptococcus Mutans ◽  
Polymorphonuclear Leukocytes ◽  
The Other ◽  
Wild Type ◽  
Transmission Electron ◽  
Specific Polysaccharide ◽  
Human Pmns ◽  
Human Polymorphonuclear Leukocytes

ABSTRACT To clarify the role of cell surface components ofStreptococcus mutans in resistance to phagocytosis by human polymorphonuclear leukocytes (PMNs), several isogenic mutants ofS. mutans defective in cell surface components were studied with a luminol-enhanced chemiluminescence (CL) assay, a killing assay, and a transmission electron microscope. The CL responses of human PMNs to mutant Xc11 defective in a major cell surface antigen, PAc, and mutant Xc16 defective in two surface glucosyltransferases (GTF-I and GTF-SI) were the same as the response to the wild-type strain, Xc. In contrast, mutant Xc24R, which was defective in serotype c-specific polysaccharide, induced a markedly higher CL response than the other strains. The killing assay showed that human PMNs killed more Xc24R than the parent strain and the other mutants. The transmission electron microscopic observation indicated that Xc24R cells were more internalized by human PMNs than the parental strain Xc. These results may be reflected by the fact that strain Xc24R was more phagocytosed than strain Xc. The CL response of human PMNs to a mutant defective in polysaccharide serotype e or f was similar to the response to Xc24R. Furthermore, mutants defective in serotype-specific polysaccharide were markedly more hydrophobic than the wild-type strains and the other mutants, suggesting that the hydrophilic nature of polysaccharides may protect the bacterium from phagocytosis. We conclude that the serotype-specific polysaccharide, but not the cell surface proteins on the cell surface of S. mutans, may play an important role in the resistance to phagocytosis.

scholarly journals Novel biphasic role for lymphocytes revealed during resolving inflammation

Blood ◽  
2008 ◽  
Vol 111 (8) ◽  
pp. 4184-4192 ◽  
Author(s):  
Ravindra Rajakariar ◽  
Toby Lawrence ◽  
Jonas Bystrom ◽  
Mark Hilliard ◽  
Paul Colville-Nash ◽  
...  
Keyword(s):  
Polymorphonuclear Leukocytes ◽  
Acute Inflammation ◽  
Secondary Infection ◽  
Receptor Activation ◽  
Innate Immune ◽  
Prostaglandin D2 ◽  
Wild Type ◽  
Secondary Challenge ◽  
Cytokine Synthesis ◽  
Regulatory Properties

Abstract Acute inflammation is traditionally described as the influx of polymorphonuclear leukocytes (PMNs) followed by monocyte-derived macrophages, leading to resolution. This is a classic view, and despite subpopulations of lymphocytes possessing innate immune-regulatory properties, seldom is their role in acute inflammation and its resolution discussed. To redress this we show, using lymphocyte-deficient RAG1−/− mice, that peritoneal T/B lymphocytes control PMN trafficking by regulating cytokine synthesis. Once inflammation ensues in normal mice, lymphocytes disappear in response to DP1 receptor activation by prostaglandin D2. However, upon resolution, lymphocytes repopulate the cavity comprising B1, natural killer (NK), γ/δ T, CD4+/CD25+, and B2 cells. Repopulating lymphocytes are dispensable for resolution, as inflammation in RAG1−/− and wild-type mice resolve uniformly. However, repopulating lymphocytes are critical for modulating responses to superinfection. Thus, in chronic granulomatous disease using gp91phox−/− mice, not only is resolution delayed compared with wild-type, but there is a failure of lymphocyte re-appearance predisposing to exaggerated immune responses upon secondary challenge that is rescued by resolution-phase lymphocytes. In conclusion, as lymphocyte repopulation is also evident in human peritonitis, we hereby describe a transition in T/B cells from acute inflammation to resolution, with a central role in modulating the severity of early onset and orchestrating responses to secondary infection.

scholarly journals BrkA Protein of Bordetella pertussisInhibits the Classical Pathway of Complement after C1 Deposition

2001 ◽  
Vol 69 (5) ◽  
pp. 3067-3072 ◽  
Author(s):  
Michael G. Barnes ◽  
Alison A. Weiss
Keyword(s):  
Western Blotting ◽  
Complement Activation ◽  
Type Strain ◽  
Wild Type Strain ◽  
Membrane Attack Complex ◽  
Enzyme Linked Immunosorbent Assay ◽  
Classical Pathway ◽  
Wild Type ◽  
Complement Proteins ◽  
Serum Killing

ABSTRACT Bordetella pertussis produces a 73-kDa protein,BrkA (Bordetella resistance to killing), which inhibits the bactericidal activity of complement. In this study we characterized the step in the complement cascade where BrkA acts, using three strains: a wild-type strain, a strain containing an insertional disruption of brkA, and a strain containing two copies of the brkA locus. Following incubation with 10% human serum, killing was greatest for the BrkA mutant, followed by that for the wild-type strain, while the strain with two copies ofbrkA was the most resistant. Complement activation was monitored by enzyme-linked immunosorbent assay (ELISA) or Western blotting. ELISAs for SC5b-9, the soluble membrane attack complex, showed that production of SC5b-9 was greatest with thebrkA mutant, less with the wild type, and least with the strain containing two copies of brkA. Deposition of complement proteins on the bacteria was monitored by Western blotting. A decrease in deposition on the bacteria of C4, C3, and C9 corresponded with decreased complement sensitivity. Deposition of C1, however, was not affected by the presence of BrkA. These studies show that BrkA inhibits the classical pathway of complement activation and prevents accumulation of deposited C4.

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