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Infection and Immunity, November 1999, p. 5762-5767, Vol. 67, No. 11
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Upregulation of p75 Tumor Necrosis Factor Alpha Receptor in Mycobacterium avium-Infected Mice: Evidence for a Functional Role

Angelo Corti,1 Lanfranco Fattorini,2 Ove Fredrik Thoresen,2 Maria Luisa Ricci,2 Anna Gallizia,1 Micaela Pelagi,1 Yongjun Li,2 and Graziella Orefici2,*

DIBIT, San Raffaele H Scientific Institute, Milan,1 and Laboratory of Bacteriology and Medical Mycology, Istituto Superiore di Sanità, Rome,2 Italy

Received 5 May 1999/Returned for modification 29 June 1999/Accepted 9 August 1999

The bacterial growth and the production of tumor necrosis factor alpha (TNF-alpha ) and TNF receptors (TNF-Rs) in the spleen and blood of BALB/c mice challenged with Mycobacterium avium complex (MAC) were monitored. Infection developed in two phases: the first, up to day 21, was associated with rapid MAC multiplication in the spleen and a drop in the mycobacteremia, and the second was associated with control of the infection in both compartments. In the spleen, TNF-alpha and TNF-RII mRNA levels peaked on day 21 and then slowly decreased; however, no increase in the level of TNF-RI mRNA was observed throughout these experiments. The level of circulating soluble TNF-RII (sTNF-RII) was transiently increased after day 21. In a model in which overproduction of bioactive TNF-alpha was triggered in response to a second infection with MAC, an increased production of sTNF-RII by cultured splenocytes was also observed. Administration of an antagonist anti-TNF-RII monoclonal antibody (MAb 6G1) to infected mice inhibited the bacterial growth in the spleen, suggesting that the TNF-RII and/or sTNF-RII was functionally involved in the mechanisms that control the infection. Overall, these observations suggest that upregulation of TNF-RII or sTNF-RII contributes to modulation of the TNF-alpha antibacterial activity in MAC infections.


* Corresponding author. Mailing address: Laboratory of Bacteriology and Medical Mycology, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy. Phone: 39 06 49902333. Fax: 39 06 49387112. E-mail: marella{at}iss.it.


Infection and Immunity, November 1999, p. 5762-5767, Vol. 67, No. 11
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.



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