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Infection and Immunity, July 2001, p. 4590-4599, Vol. 69, No. 7
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.7.4590-4599.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Gram-Positive and Gram-Negative Bacteria Do Not Trigger Monocytic Cytokine Production through Similar Intracellular Pathways

Lila Rabehi, Théano Irinopoulou, Béatrice Cholley, Nicole Haeffner-Cavaillon, and Marie-Paule Carreno*

INSERM U430, Hôpital Broussais, and Université Pierre et Marie Curie, Paris, France

Received 20 September 2000/Returned for modification 19 January 2001/Accepted 26 March 2001

Toll-like receptors (TLRs) are involved in human monocyte activation by lipopolysaccharide (LPS) and Staphylococcus aureus Cowan (SAC), suggesting that gram-positive and gram-negative bacteria may trigger similar intracellular events. Treatment with specific kinase inhibitors prior to cell stimulation dramatically decreased LPS-induced cytokine production. Blocking of the p38 pathway prior to LPS stimulation decreased interleukin-1alpha (IL-1alpha ), IL-1ra, and tumor necrosis factor alpha (TNF-alpha ) production, whereas blocking of the ERK1/2 pathways inhibited IL-1alpha , IL-1beta , and IL-1ra but not TNF-alpha production. When cells were stimulated by SAC, inhibition of the p38 pathway did not affect cytokine production, whereas only IL-1alpha production was decreased in the presence of ERK kinase inhibitor. We also demonstrated that although LPS and SAC have been shown to bind to CD14 before transmitting signals to TLR4 and TLR2, respectively, internalization of CD14 occurred only in monocytes triggered by LPS. Pretreatment of the cells with SB203580, U0126, or a mixture of both inhibitors did not affect internalization of CD14. Altogether, these results suggest that TLR2 signaling does not involve p38 mitogen-activated protein kinase signaling pathways, indicating that divergent pathways are triggered by gram-positive and gram-negative bacteria, thereby inducing cytokine production.

* Corresponding author. Mailing address: INSERM U430, 96 rue Didot, 75674 Paris Cedex, France. Phone: 33 1 43 95 95 67. Fax: 33 1 45 45 90 59. E-mail: marie-paule.carreno{at}brs.ap-hop-paris.fr.

Infection and Immunity, July 2001, p. 4590-4599, Vol. 69, No. 7
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.7.4590-4599.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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