Comparative role of complement in pneumococcal and staphylococcal pneumonia

Coonrod, J D; Yoneda, K

doi:10.1128/iai.37.3.1270-1277.1982

Cited by 19 publications

(6 citation statements)

References 17 publications

(20 reference statements)

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“…Moreover, compared to controls, complementdepleted guinea pigs were killed by smaller numbers of pneumococci (5). In another study of pneumococcal pneumonia in rats, complement depletion with cobra venom factor led to an increase in the numbers of pneumococci in their lungs at 24 h postinfection (7). Cobra venom factor treatment commonly reduces the hemolytic complement levels in experimental animals to only 0.1 to 1% of normal values (11).…”

Section: Discussionmentioning

confidence: 99%

Role of Pneumolysin’s Complement-Activating Activity during Pneumococcal Bacteremia in Cirrhotic Rats

1999

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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 × 107 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 PLY− strain. Furthermore, the mortality rate for control and cirrhotic rats was identical after infection with the H+C− strain. These studies suggest that pneumolysin production contributes to decreased pneumococcal clearance from the bloodstream and higher mortality in both control and cirrhotic rats. However, pneumolysin’s complement-activating activity may uniquely enhance pneumococcal virulence in the hypocomplementemic, cirrhotic host.

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Section: Discussionmentioning

confidence: 99%

Role of Pneumolysin’s Complement-Activating Activity during Pneumococcal Bacteremia in Cirrhotic Rats

1999

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“…The alternative complement pathway is critically important for its ability to amplify complement activity ( 3 , 4 ) and for its role in the hyperacute response to infection ( 5 ), including host defense in the lung ( 6 , 7 ). Biological stressors, including infection ( 8 – 11 ), ischemia ( 12 ), trauma ( 13 , 14 ), burns ( 15 ), and surgery ( 16 , 17 ), have all been noted to activate the human complement system.…”

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confidence: 99%

Increased Alternative Complement Pathway Function and Improved Survival during Critical Illness

Bain

Geest

et al. 2020

Am J Respir Crit Care Med

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Rationale: Complement is crucial for host defense but may also drive dysregulated inflammation. There is limited understanding of alternative complement function, which can amplify all complement activity, during critical illness. Objectives: We examined the function and key components of the alternative complement pathway in a series of critically ill patients and in a mouse pneumonia model. Methods: Total classical (CH50) and alternative complement (AH50) function were quantified in serum from 321 prospectively enrolled critically ill patients and compared with clinical outcomes. Alternative pathway (AP) regulatory factors were quantified by ELISA ( n = 181) and examined via transcriptomics data from external cohorts. Wild-type, Cfb −/− , and C3 −/− mice were infected intratracheally with Klebsiella pneumoniae (KP) and assessed for extrapulmonary dissemination. Measurements and Main Results: AH50 greater than or equal to median, but not CH50 greater than or equal to median, was associated with decreased 30-day mortality (adjusted odds ratio [OR], 0.53 [95% confidence interval (CI), 0.31–0.91]), independent of chronic liver disease. One-year survival was improved in patients with AH50 greater than or equal to median (adjusted hazard ratio = 0.59 [95% CI, 0.41–0.87]). Patients with elevated AH50 had increased levels of AP factors B, H, and properdin, and fewer showed a “hyperinflammatory” subphenotype (OR, 0.30 [95% CI, 0.18–0.49]). Increased expression of proximal AP genes was associated with improved survival in two external cohorts. AH50 greater than or equal to median was associated with fewer bloodstream infections (OR, 0.67 [95% CI, 0.45–0.98). Conversely, depletion of AP factors, or AH50 less than median, impaired in vitro serum control of KP that was restored by adding healthy serum. Cfb −/− mice demonstrated increased extrapulmonary dissemination and serum inflammatory markers after intratracheal KP infection compared with wild type. Conclusions: Elevated AP function is associated with improved survival during critical illness, possibly because of enhanced immune capacity.

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“…There is substantial evidence that serum complement plays an important role in host resistance to pneumococcal infections (4,6,16). Maximal opsonization of pneumococci requires an intact classical and alternate complement pathway, and thus complement deficiency can result in an inability to clear these organisms (6,8,16).…”

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confidence: 99%

Activation of human complement by the pneumococcal toxin pneumolysin

Paton¹,

Rowan-Kelly²,

Fèrrante³

1984

Infect Immun

191

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Highly purified pneumolysin (at a concentration of 10 ,ug/ml) caused significant activation of human complement, as measured by conversion of C3. Complement activation in the presence of pneumolysin was not observed in sera chelated with a combination of Mg2' and ethylene glycol-bis(P-aminoethyl ether)-N,N-This work was supported by grants from the National Health and Medical Research Council and the Adelaide Children's Hospital Research Trust. LITERATURE CITED 1. Bradford, M. M. 1976. A rapid and sensitive method for the quantitation of microgram quantities of protein using the princi

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Comparative role of complement in pneumococcal and staphylococcal pneumonia

Cited by 19 publications

References 17 publications

Role of Pneumolysin’s Complement-Activating Activity during Pneumococcal Bacteremia in Cirrhotic Rats

Role of Pneumolysin’s Complement-Activating Activity during Pneumococcal Bacteremia in Cirrhotic Rats

Increased Alternative Complement Pathway Function and Improved Survival during Critical Illness

Activation of human complement by the pneumococcal toxin pneumolysin

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