Streptococcus pneumoniae and Streptococcus agalactiae cause distinct infectious diseases in small children. Similarly, these bacteria elicit very different host-cell responses in vitro. Inactivated S. agalactiae by far exceeds S. pneumoniae in the activation of inflammatory cytokines and upstream signaling intermediates such as the MAP kinase JNK. The inflammatory response to both Streptococcus spp. is mediated by MyD88, an essential adapter protein of Toll-like receptors (TLRs), although the specific TLRs that are involved have not been fully resolved. Furthermore, during logarithmic growth, S. pneumoniae releases pneumolysin that interacts with TLR4 whereas S. agalactiae releases diacylated molecules that interact with TLR2/6. Interaction of these soluble bacterial products with their cognate TLRs is critical for limiting bacterial dissemination and and systemic inflammation in mice. This might be due, in part, to TLR-mediated apoptosis induced by these factors. In conclusion related streptococcal species induce specific events in TLR-mediated signal transduction. Comparative analysis of the host-cell response to these bacteria reveals molecules such as JNK as valuable targets for adjunctive sepsis therapy.
Moore MR, Schrag SJ, Schuchat A.Effects of intrapartum antimicrobial prophylaxis for prevention of group-B-streptococcal disease on the incidence and ecology of early-onset neonatal sepsis. Lancet Infect Dis2003; 3: 201—213.
6.
Malley R., Henneke P., Morse SC et al. Recognition of pneumolysin by Toll-like receptor 4 confers resistance to pneumococcal infection. Proc Natl Acad Sci USA2003; 100: 1966—1971.
7.
Steenhoff AP , Shah SS, Ratner AJ, Patil SM, McGowan KLEmergence of vaccine-related pneumococcal serotypes as a cause of bacteremia. Clin Infect Dis2006; 42: 907—914.
8.
Palazzi DL, Rench MA, Edwards MS, Baker CJUse of type V group B streptococcal conjugate vaccine in adults 65—85 years old. J Infect Dis2004; 190: 558—564.
9.
Hyde TB, Hilger TM, Reingold A. et al. Trends in incidence and antimicrobial resistance of early-onset sepsis: population-based surveillance in San Francisco and Atlanta. Pediatrics2002; 110: 690—695.
10.
Zaleznik DF , Rench MA, Hillier S. et al. Invasive disease due to group B streptococcus in pregnant women and neonates from diverse population groups. Clin Infect Dis2000; 30: 276—281.
11.
Schuchat A. , Hilger T., Zell E. et al. Active bacterial core surveillance of the emerging infections program network. Emerg Infect Dis2001; 7: 92—99.
12.
Heath PT, Balfour G., Weisner AM et al. Group B streptococcal disease in UK and Irish infants younger than 90 days. Lancet2004; 363: 292—294.
Draper DW, Bethea HN, He Y-W.Toll-like receptor 2-dependent and independent activation of macrophages by group B streptococci. Immunol Lett2006; 102: 202—214.
15.
Henneke P., Takeuchi O., van Strijp JA et al. Novel engagement of CD14 and multiple Toll-like receptors by group B streptococci. J Immmunol2001; 167: 7069—7076.
16.
Henneke P., Takeuchi O., Malley R. et al. Cellular activation, phagocytosis, and bactericidal activity against group B streptococcus involve parallel myeloid differentiation factor 88-dependent and independent signaling pathways. J Immunol2002; 169: 3970—3977.
17.
Kenzel S., Mancuso G., Malley R. et al. c-Jun kinase is a critical signaling molecule in a neonatal model of group B streptococcal sepsis. J Immunol2006; 176: 3181—3188.
18.
Mancuso G., Midiri A., Beninati C. et al. Dual role of TLR2 and myeloid differentiation factor 88 in a mouse model of invasive group B streptococcal disease. J Immunol2004; 172: 6324—6329.
19.
Yoshimura A. , Lien E., Ingalls RR et al. Recognition of Gram-positive bacterial cell wall components by the innate immune system occurs via Toll-like receptor 2. J Immunol1999; 163: 1—5.
20.
Flo TH, Halaas O., Lien E. et al. HumanToll-like receptor 2 mediates monocyte activation by Listeria monocytogenes, but not by group B streptococci or lipopolysaccharide. J Immunol2000; 164: 2064—2069.
21.
Koedel U., Angele B., Rupprecht T. et al. Toll-like receptor 2 participates in mediation of immune response in experimental pneumococcal meningitis. J Immunol2003; 170: 438—444.
22.
Malley R., Henneke P., Morse SC et al. Recognition of pneumolysin by Toll-like receptor 4 confers resistance to pneumococcal infection. Proc Natl Acad Sci USA2003; 100: 1966—1971.
23.
Srivastava A., Henneke P., Visintin A. et al. The apoptotic response to pneumolysin is Toll-like receptor 4 dependent and protects against pneumococcal disease . Infect Immun2005; 73: 6479—6487.
24.
Branger J., Knapp S., Weijer S. et al. Role of Toll-like receptor 4 in Gram-positive and Gram-negative pneumonia in mice. Infect Immun2004; 72: 788—794.
25.
Fichorova RN , Cronin AO, Lien E., Anderson DJ, Ingalls RRResponse to Neisseria gonorrhoeae by cervicovaginal epithelial cells occurs in the absence of Toll-like receptor 4-mediated signaling . J Immunol2002; 168: 2424—2432.
26.
Fransson M. , Adner M., Erjefalt J. et al. Up-regulation of Toll-like receptors 2, 3 and 4 in allergic rhinitis. Respir Res2005; 6: 100.
27.
Navarre WW, Schneewind O.Surface proteins of Gram-positive bacteria and mechanisms of their targeting to the cell wall envelope. Microbiol Mol Biol Rev1999; 63: 174—229.
28.
Deng L., Kasper DL, Krick TP, Wessels MRCharacterization of the linkage between the type III capsular polysaccharide and the bacterial cell wall of group B streptococcus. J Biol Chem2000; 275: 7497—7504.
29.
Schleifer KH , Kandler O.Peptidoglycan types of bacterial cell walls and their taxonomic implications. Bacteriol Rev1972; 36: 407—477.
30.
Severin A., Tomasz A.Naturally occurring peptidoglycan variants of Streptococcus pneumoniae. J Bacteriol1996; 178: 168—174.
31.
Moreillon P., Majcherczyk PAProinflammatory activity of cell-wall constituents from Gram-positive bacteria . Scand J Infect Dis2003; 35: 632—641.
32.
Takeuchi O., Kawai T., Muhlradt PF et al. Discrimination of bacterial lipoproteins by Toll-like receptor 6. Int Immunol2001; 13: 933—940.
33.
Majcherczyk PA , Langen H., Heumann D. et al. Digestion of Streptococcus pneumoniae cell walls with its major peptidoglycan hydrolase releases branched stem peptides carrying proinflammatory activity. J Biol Chem1999; 274: 12537—12543.
34.
Travassos LH, Girardin SE, Philpott DJ et al. Toll-like receptor 2-dependent bacterial sensing does not occur via peptidoglycan recognition. EMBO Report2004; 5: 1000-1006.
35.
Girardin SE , Tournebize R., Mavris M. et al. CARD4/Nod1 mediates NF-kappaB and JNK activation by invasive Shigella flexneri. EMBO Report2001; 2: 736—742.
36.
Girardin SE , Boneca IG, Carneiro LA et al. Nod1 detects a unique muropeptide from Gram-negative bacterial peptidoglycan. Science2003; 300: 1584—1587.
37.
Dziarski R. , Gupta D.Staphylococcus aureus peptidoglycan is a Toll-like receptor 2 activator: a re-evaluation. Infect Immun2005; 73: 5212—5216.
38.
Henneke P., Morath S., Uematsu U. et al. Role of lipoteichoic acid in the phagocyte response to group B streptococcus. J Immunol2005; 174: 6449—6455.
39.
Han SH, Kim JH, Martin M., Michalek SM, Nahm MHPneumococcal lipoteichoic acid (LTA) is not as potent as staphylococcal LTA in stimulating Toll-like receptor 2. Infect Immun2003; 71: 5541—5548.
40.
Morath S., Geyer A., Hartung T.Structure—function relationship of cytokine induction by lipoteichoic acid from Staphylococcus aureus. J Exp Med2001; 193: 393—397.
41.
Morath S., Stadelmaier A., Geyer A., Schmidt RR, Hartung T.Synthetic lipoteichoic acid from Staphylococcus aureus is a potent stimulus of cytokine release. J Exp Med2002; 195: 1635—1640.
42.
Poyart C., Pellegrini E., Marceau M. et al. Attenuated virulence of Streptococcus agalactiae deficient in D-alanyl-lipoteichoic acid is due to an increased susceptibility to defensins and phagocytic cells. Mol Microbiol2003; 49: 1615—1625.
43.
Grangette C. , Nutten S., Palumbo E. et al. Enhanced antiinflammatory capacity of a Lactobacillus plantarum mutant synthesizing modified teichoic acids. Proc Natl Acad Sci USA2005; 102: 10321—10326.
44.
Fluegge K., Supper S., Siedler A., Berner R.Serotype distribution of invasive group B streptococcal isolates in infants: results from a nationwide active laboratory surveillance study over 2 years in Germany. Clin Infect Dis2005; 40: 760—763.
45.
Lehnardt S. , Henneke P., Lien E. et al. A mechanism for neurodegeneration induced by group B streptococci through activation of the TLR2/MyD88 pathway in microglia . J Immunol2006; 177: 583—592.
46.
Halaas O., Liabakk NB, Vik R. et al. Monocytes stimulated with group B streptococci or interferons release tumour necrosis factor-related apoptosis-inducing ligand. Scand J Immunol2004; 60: 74—81.
47.
Liu GY, Doran KS, Lawrence T. et al. Sword and shield: linked group B streptococcal beta-hemolysin/cytolysin and carotenoid pigment function to subvert host phagocyte defense. Proc Natl Acad Sci USA2004; 101: 14491—14496.
48.
Ebert S., Gerber J., Bader S. et al. Dose-dependent activation of microglial cells by Toll-like receptor agonists alone and in combination. J Neuroimmunol2005; 159: 87—96.
49.
van Rossum AM , Lysenko ES, Weiser JNHost and bacterial factors contributing to the clearance of colonization by Streptococcus pneumoniae in a murine model . Infect Immun2005; 73: 7718—7726.
50.
Bermpohl D. , Halle A., Freyer D. et al. Bacterial programmed cell death of cerebral endothelial cells involves dual death pathways. J Clin Invest2005; 115: 1607—1615.
