Bacterial lipoteichoic acid sensitizes host cells for destruction by autologous complement.

Abstract

Lipoteichoic acids (LTA) released by gram-positive bacteria can spontaneously bind to mammalian cell surfaces. In the present study, erythrocytes (E) sensitized with pneumococcal LTA (LTA-E) were used as a model system to determine if LTA could render host cells susceptible to damage by autologous complement.Complement (C)-mediated lysis of LTA-E from normal rats and normal humans occurred when these cells were incubated in their respective autologous sera in vitro. In addition, when LTA-E from a C2-deficient human and from C4-deficient guinea pigs were incubated in their autologous sera, there was significant lysis in vitro, demonstrating a role for the alternative pathway. The in vivo survival of 51Cr-labeled autologous LTA-E was also studied. Only 2.9% of autologous LTA-E remained in the circulation of normal rats after 90 min. In contrast, 31.2% of autologous LTA-E remained in the circulation of rats depleted of C3. Intravascular hemolysis accounted for the clearance of LTA-E in the normal rats, whereas liver sequestration was responsible for clearance in the C3-depleted rats. These results demonstrate that LTA can render the host's cells susceptible to damage by its own complement system, establishing this as a possible mechanism of tissue damage in natural bacterial infections.

Lipoteichoic acid-antilipoteichoic acid complexes induce superoxide generation by human neutrophils

“…These findings suggest that although the Fc portion of the immunoglobulin might be unengaged, complement might not be activated under the conditions of our experiments. On the other hand, the findings that LTAanti-LTA complexes not bound to cells readily activate complement (26,27) and that complement activation resulted in the death of a variety of LTA-sensitized target cells (fibroblasts, tumor cells, and RBCs) (19,22,23) indicate that further studies to elucidate this controversial finding should be performed.…”

“…Since LTA-anti-LTA complexes activate complement via the classical and alternative pathways (26,77) and also since distinct cytopathic changes were induced in LTA-sensitized target cells which had been treated with complement-sufficient anti-LTA sera (19,22,23), it was also of interest to examine the possibility that complement activation might also enhance superoxide generation. In preliminary experiments performed in collaboration with Dr. G. Till, it was found that the addition of either human or guinea pig serum containing 10-20 CHso units of complement to LTA-sensitized PMNs in the presence of anti-LTA globulin did not result in a significant enhancement of superoxide generation.…”

“…Red blood cells that had been presensitized with LTA undergo very strong agglutination (4)(5)(6)(7)(8)(9)(19)(20)(21) and lysis (19,(20)(21)(22)(23) following treatment with anti-LTA antibodies plus serum complement (complement-dependent cellular cytotoxicity or passive immune kill). Antibodies to LTA are found in the IgM and IgG fraction of serum (20).…”

A Continuum of Anionic Charge: Structures and Functions ofd-Alanyl-Teichoic Acids in Gram-Positive Bacteria

“…In this context, TAs function as inducers of proinflammatory mediators, immunogens, complement activators, adhesins, and mitogens (158,180,232,471). Our goal in this review is to summarize the host responses where the D-alanyl esters of TAs are implicated.…”

Lipoteichoic acid fractions from pathogenic and apathogenic Listeria species and Staphylococcus aureus induce similar amounts of macrophage-derived cytokines

“…Furthermore, other serumfactors, e.g. albumin [23] and complement [24] have been shown to either reduce binding ofLTAs to eurkaryotic cells orto induce lysis ofcells sensitized with LTAs. To avoid the effect of serum factors we used a serum-free system for the induction of cytokines and proliferation.…”