Differential effects of TNF and LT alpha in the host defense against M-bovis BCG

Citation
M. Bopst et al., Differential effects of TNF and LT alpha in the host defense against M-bovis BCG, EUR J IMMUN, 31(6), 2001, pp. 1935-1943
Citations number
47
Categorie Soggetti
Immunology
Journal title
EUROPEAN JOURNAL OF IMMUNOLOGY
ISSN journal
00142980 → ACNP
Volume
31
Issue
6
Year of publication
2001
Pages
1935 - 1943
Database
ISI
SICI code
0014-2980(200106)31:6<1935:DEOTAL>2.0.ZU;2-D
Abstract
Signaling via TNF receptor type 1 (TNFR1) was shown to be crucial in host d efense against the intracellular pathogens L. monocytogenes, M. tuberculosi s and M. bovis. To investigate the function of TNF and LT alpha in host def ense against M. bovis, mice double deficient for TNF and LT alpha (TNF/LT a lpha (-/-)), TNF/LT alpha (-/-) mice complemented with a murine LT alpha tr ansgene (TNF-/-) and LT alpha (-/-) mice were infected with BCG and the ens uing pathology was investigated. Control mice showed a normal host defense with early clearance of bacteria. The granulomatous reaction in the liver w as accompanied by recruitment of activated macrophages characterized by the ir acid phosphatase positivity and differentiation into epithelioid cells a s well as a coordinated expression of proinflammatory transcripts. In contr ast, TNF/LT alpha (-/-) mice showed no comparable recruitment of activated macrophages in the liver. Furthermore, these mice showed extensive necrotic pulmonary lesions with massive growth of acid fast bacilli. Reintroduction of LT alpha as a transgene into TNF/LT alpha (-/-) mice prolonged survival but did not restore resistance to BCG. This, at least partially protective role of LT alpha was further supported by data demonstrating that LT alpha -deficient mice as well were susceptible to BCG infection. In contrast to the deleterious effect of TNF/LT alpha deficiency in BCG infection, BCG-inf ected TNF/LT alpha (-/-) mice were tolerant to LPS-induced shock. These res ults demonstrate that TNF as well as LT alpha are involved in murine host d efense against BCG and that absence of TNF/LT alpha protects BCG-infected m ice from LPS mediated shock.