Pneumolysin induced complement depletion during experimental pneumococcal bacteremia. (2001 May)
pneumolysin induced complement depletion during experimental pneumococcal bacteremia . To quantify complement depletion by pneumolysin during streptococcus pneumoniae bacteremia , cirrhotic and control rats were infected intravenously with one of three isogenic mutant strains of S . pneumoniae expressing different forms of pneumolysin . outcome measures included clearance of the organisms from the bloodstream , alterations in 50 serum hemolytic complement ( CH ( 50 ) ) activity and complement C3 levels during infection , and serum opsonic capacity at 18 h postinfection . cirrhotic rats had significantly lower CH ( 50 ) and C3 levels than control rats , both before and after infection . however , initial complement levels did not predict bacterial load after 18 h of infection . changes in CH ( 50 ) and C3 levels over the 18 h period correlated with numbers of H C but not H C or PLY organisms in the bloodstream at 18 h postinfection . The sera of cirrhotic rats infected with the H C strain had significantly decreased levels of C3 and showed significantly lower opsonizing activity for S . pneumoniae than sera from H C infected control rats . these studies suggest that under limiting concentrations of complement , the expression of pneumolysin by pneumococci has a significant , negative effect on serum complement levels and reduces serum opsonic activity .

Factor H binding to PspC of streptococcus pneumoniae increases adherence to human cell lines in vitro and enhances invasion of … (2007 Jul)
factor H binding to PspC of streptococcus pneumoniae increases adherence to human cell lines in vitro and enhances invasion of mouse lungs in vivo . pneumococcal surface protein C ( PspC ) binds to both human secretory immunoglobulin A ( sIgA ) and complement factor H ( FH ) . FH , a regulator of the alternative pathway of complement , can also mediate adherence of different host cells . since PspC contributes to adherence and invasion of host cells , we hypothesized that the interaction of PspC with FH may also mediate adherence of pneumococci to human cells . In this study , we investigated FH and sIgA mediated pneumococcal adherence to human cell lines in vitro . adherence assays demonstrated that preincubation of streptococcus pneumoniae D39 with FH increased adherence to human umbilical vein endothelial cells ( huvec ) 5 fold and to lung epithelial cells ( SK MES 1 ) 18 fold , relative to that of D39 without FH on the surface . The presence of sIgA enhanced adherence to SK MES 1 6 fold and to pharyngeal epithelial cells ( detroit 562 ) 14 fold . furthermore , sIgA had an additive effect on adherence to huvec ; specifically , preincubation of D39 with both FH and sIgA led to a 21 fold increase in adherence . finally , using a mouse model , we examined the significance of the FH PspC interaction in pneumococcal nasal colonization and lung invasion . Mice intranasally infected with …

Participation of complement in the nonimmune host defense against experimental haemophilus influenzae type b septicemia and meningitis. (1977 Jan)
participation of complement in the nonimmune host defense against experimental haemophilus influenzae type b septicemia and meningitis . This study was undertaken to determine whether the terminal complement components ( C3 9 ) are involved in the nonimmune host defense against haemophilus influenzae type b septicemia and meningitis . using cobra venom factor , infant rats were depleted of C3 and C5 . after intranasal challenge with H . influenzae type b , the complement depleted rats developed a greater incidence and magnitude of bacteremia and a higher mortality rate . In contrast to the effects on bacteremia , complement depletion did not directly influence either the occurrence of meningitis or bacterial multiplication within the cerebrospinal fluid . these experiments provide evidence that the complement system may be an important mechanism of natural immunity to H . influenzae type b .

Participation of complement in host defense against encapsulated haemophilus influenzae types a , c , and d. (1982 Jun)
participation of complement in host defense against encapsulated haemophilus influenzae types a , c , and d . Each of the serotypes of haemophilus influenzae ( types a to f ) may colonize the respiratory tract of humans , but only type b strains commonly cause invasive systemic infections . To investigate the role of complement in immunity to encapsulated non type b strains , rats were depleted of C3 with cobra venom factor and challenged with representative serotypes of H . influenzae ( type a , b , c , or d ) by different routes . after intravenous challenge , rats depleted of C3 had a greater incidence and magnitude of bacteremia with each of the serotypes when compared with normal controls . intraperitoneal inoculation of type b organisms resulted in meningitis in normal and C3 depleted rats , but only C3 depleted , and not normal , rats developed meningitis after inoculation of serotype a , c , or d . In contrast to systemic inoculation , intranasal challenge with the different serotypes resulted in bloodstream invasion and meningitis only after challenge with type b organisms . these data suggest that complement plays a significant role in immunity to encapsulated , non type b H . influenzae through its effect on bloodstream clearance .

Role of complement receptors 1 and 2 ( CD35 and CD21 ) , C3 , C4 , and C5 in … (2004 Jun)
Role of complement receptors 1 and 2 ( CD35 and CD21 ) , C3 , C4 , and C5 in survival by mice of staphylococcus aureus bacteremia . complement mediated opsonization and phagocytosis of encapsulated serotype 5 staphylococcus aureus are essential to host defense . We describe the effects of complement depletion and deficiencies of C4 , C5 , and complement receptors 1 and 2 on mouse survival after intravenous exposure to S aureus . depletion of complement proteins in c57bl / 6 mice with the use of cobra venom factor decreased survival compared with that of controls after the induction of bacteremia with mucoid ( 90 mortality ) , encapsulated ( 73 ) , and unencapsulated ( 59 ) S aureus strains . In this model complement is even more important in the control of infection with encapsulated S aureus ( 80 of clinical isolates ) than in the control of infection by unencapsulated strains . C4 deficient mice demonstrated similar mortality from bacteremia caused by encapsulated S aureus compared with controls , suggesting that in the unimmunized animal the alternative complement pathway contributes more to control of bacteremia caused by encapsulated S aureus than the classical complement pathway or mannan binding lectin pathway . C5 deficient mice ( B10 . D2 H2 ( d ) H2 T18 ( c ) Hc ( 0 ) / oSnJ ) showed similar mortality when subjected to bacteremia caused by encapsulated S aureus compared with C5 sufficient ( B10 . D2 Hc …

In vivo binding of complement regulator factor H by streptococcus pneumoniae. (2005 Nov)
In vivo binding of complement regulator factor H by streptococcus pneumoniae . pneumococcal surface protein C ( PspC ) binds to the complement regulatory protein factor H ( FH ) , which inhibits alternative pathway activation . In the present study , using a mouse model of systemic infection and flow cytometric analyses , we demonstrated an in vivo interaction between FH and pneumococci and showed differential FH binding during bacteremia . Flow cytometric analyses of pneumococci harvested after intraperitoneal ( ip ) challenge demonstrated increased binding of FH , compared with that after intravenous ( iv ) challenge . Real time polymerase chain reaction analyses of PspC mRNA showed that , relative to pneumococci grown in vitro , those recovered from the blood of mice 24 h after iv challenge exhibited 23 fold higher mRNA levels ; however , after ip challenge , PspC mRNA induction was increased 870 fold . A subsequent increase in PspC expression was detected by flow cytometry using a monoclonal antibody against PspC . furthermore , pneumococci with FH bound to complement before exposure had increased proliferation , compared with pneumococci not pretreated with FH . these results suggest that the interaction between PspC and FH contributes to pneumococcal virulence .

Complement factor H binding protein , a putative virulence determinant of borrelia hermsii , is an antigenic target for protective … (2008 Mar)
complement factor H binding protein , a putative virulence determinant of borrelia hermsii , is an antigenic target for protective B1b lymphocytes . vaccination is the most effective way to control infectious diseases . A variety of microbial pathogens use antigenic variation , an immune evasion strategy that poses a challenge for vaccine development . To understand protective immune responses against such pathogens , we have been studying borrelia hermsii , a bacterium that causes recurrent bacteremia due to antigenic variation . An IgM response is necessary and sufficient to control B . hermsii infection . We have recently found a selective expansion of B1b cells concurrent with the resolution of B . hermsii bacteremia . B1b cells from convalescent but not naive mice confer long lasting immunity , but the Ag ( s ) driving the protective IgM responses is unknown . herein we demonstrate that convalescent B1b cell derived IgM recognizes complement factor H binding protein ( FhbA ) , a B . hermsii outer surface protein and putative virulence factor that does not undergo antigenic variation and is expressed by all clinical isolates . A progressive increase in the IgM response to FhbA correlated with the kinetics of B1b cell expansion , diminished the severity of bacteremic episodes , and led to the eventual resolution of the infection . these data indicate that FhbA is a specific target for protective B1b cell responses . Ags recognized by B1b cells may be considered as an important component in …

Inhibition of interleukin 6 synthesis in an animal model of septic shock by anti C5a monoclonal antibodies. (1996 Jul)
inhibition of interleukin 6 synthesis in an animal model of septic shock by anti C5a monoclonal antibodies . The complement activation fragment C5a was recently shown to induce interleukin ( IL ) 6 synthesis by peripheral blood mononuclear cells . To understand better the role of C5a in cytokine regulation in vivo , we investigated the effects of complement depletion by cobra venom factor ( CVF ) or of anti C5a monoclonal antibodies ( mAb ) on IL 6 generation in an animal model of septic shock . complement depleted pigs which were subsequently challenged with escherichia coli generated significantly ( p 0 . 05 ) less IL 6 during the 6 h observation period than complement sufficient controls . To address specifically the role of C5a in IL 6 regulation , we produced a C5a ( 57 74 ) peptide specific mAb ( T13 / 9 ) which neutralizes the bioactivity of porcine C5a . The mAb T13 / 9 does not cross react with the precursor protein C5 . The pretreatment of pigs with anti C5a mAb T13 / 9 prior to the induction of sepsis resulted in a decrease of over 75 in serum IL 6 bioactivity compared to control animals ( p 0 . 0001 ) . these results indicate a role for C5a in the modulation of IL 6 synthesis in Gram negative bacteremia .

Participation of complement in host defense against capsule deficient haemophilus influenzae. (1984 Jan)
participation of complement in host defense against capsule deficient haemophilus influenzae . To investigate the role of complement in immunity to capsule deficient haemophilus influenzae , rats were depleted of C3 with cobra venom factor and challenged with three different strains of capsule deficient H . influenzae . Two of them ( Rd and U1 ) did not elaborate type b capsular antigen , whereas the other ( S2 ) elaborated 0 . 16 of the amount made by its type b parent strain . depletion of C3 significantly enhanced early intravascular bacterial survival after intravenous inoculation and strikingly increased the susceptibility of rats to infection with capsule deficient H . influenzae . after intraperitoneal inoculation with strain Rd or U1 , C3 depleted rats developed bacteremia , whereas control rats did not ; challenge with strain S2 resulted in transient bacteremia in normal rats and in death in C3 depleted animals . To determine whether the greater virulence of strain S2 , as compared with strain Rd or U1 , was accounted for by the small amounts of capsular antigen it elaborated , we also compared its relative virulence to that of three genetically closely related capsule deficient variants elaborating either small amounts of type b capsule or producing no detectable b antigen . No difference in virulence was observed among these four variants ; all C3 depleted rats inoculated developed bacteremia of similar magnitude followed by similar mortality rates . these studies demonstrate a significant role for complement …

Differential complement resistance mediates virulence of haemophilus influenzae type b. (1982 Mar)
differential complement resistance mediates virulence of haemophilus influenzae type b . studies were undertaken to gain insight into the virulence of type b in contrast to the other haemophilus influenzae capsular types . A relationship was found between the comparative virulence of H . influenzae types in humans and their resistance to the bactericidal effect of antibody free complement . Type b was most resistant to the bactericidal effect of complement . The other types could be divided into three groups based upon their susceptibility to complement ; this grouping was also related to their structural similarities . No association between virulence and either the biotype , source of isolate , in vitro association with peripheral polymorphonuclear leukocytes , or the total amount of capsular polysaccharide was found . however , among the type b strains , higher levels of cell associated polysaccharide were associated with increased resistance to complement . The relative virulence of the six H . influenzae types in the infant rat model was generally similar to that in humans . after intraperitoneal challenge , type b and type a strains had the lowest 50 effective doses for bacteremia , removed by several logs from the values of the other types . By intranasal challenge , type b strains produced higher rates and levels of bacteremia than did type a strains . High levels of natural bactericidal antibodies to types c and e were found in adult female rats ; this finding alone could not account for …

Role of pneumolysin s complement activating activity during pneumococcal bacteremia in cirrhotic rats. (1999 Jun)
Role of pneumolysin s complement activating activity during pneumococcal bacteremia in cirrhotic rats . We investigated the role of pneumolysin s complement activating activity during streptococcus pneumoniae bacteremia in a hypocomplementemic , cirrhotic host . isogenic mutant pneumococcal strains , in which pneumolysin was expressed from a plasmid , were used . these strains included H C , expressing wild type pneumolysin with both cytolytic and complement activating activity ; PLY , carrying the plasmid without the pneumolysin gene ; and , H C , expressing pneumolysin with cytolytic activity only . In control rats , intravenous infection with 2 . 0 x 10 ( 7 ) CFU of H C per ml of blood resulted in a decrease in bacteremia of 3 . 5 log units by 18 h postinfection and 55 mortality . By contrast , cirrhotic rats infected similarly with the H C strain demonstrated a 0 . 2 log unit increase in bacteremia by 18 h postinfection and 100 mortality . Both control and cirrhotic rats cleared the PLY strain more effectively from their bloodstreams by 18 h postinfection ( 6 . 2 and 5 . 6 log unit decreases , respectively ) . infection with the PLY strain also resulted in low mortality ( 0 and 14 , respectively ) for control and cirrhotic rats . When infected with the H C strain ( without complement activating activity ) , both groups cleared the organism from their bloodstreams nearly as well as they did the …

Susceptibility of helicobacter pylori to the bactericidal activity of human serum. (1998 Jan)
susceptibility of helicobacter pylori to the bactericidal activity of human serum . background : human serum represents an important barrier to the entry of most mucosal organisms into tissues and to the systemic circulation . If at all present , helicobacter pylori within gastric tissue is rare , and bacteremia for this organism has been described only once . methods : To assess the susceptibility of H . pylori to the bactericidal activity present in normal human serum ( NHS ) , we examined 13 H . pylori isolates . To assess the contributions of the classical and alternative complement pathways to killing , we added either C2 deficient or factor B deficient serum , respectively , to heat inactivated NHS . Also we assessed the ability of the strains to bind 125I C3 . results : after incubation for 60 minutes at 37 degrees C , all 13 H . pylori strains were killed by NHS ; heating to 56 degrees C for 30 minutes ablated killing , indicating complement dependence for this phenomenon . In the absence of an antibody source , there was no killing when either an alternative or classical complement pathway source was used . adding B deficient serum to heat inactivated normal human serum did not restore killing , but adding C2 deficient serum permitted partial killing . All of the 13 strains bound 125I C3 . although the kinetics varied from strain to strain , C3 bound was significantly correlated ( r 0 …