K11E KI mice were protected from low-dose Listeria monocytogenes infection but only partially or not protected from high dose infection. A study of L. monocytogenes infection in memTNFD112 KI mice showed partial survival of these mice to low bacterial dose. The memTNFD19,K11E form was shown to be sufficient to develop partial innate immunity to Francisella tularensis live vaccine strain. An important role of memTNFD19,K11E was observed in the resolution of the inflammatory lesion induced by Leishmania major infection. Infection with M. tuberculosis of memTNFD19,K11E KI mice showed protection against acute but not to chronic infection. These studies confirmed our previous results on transgenic mice expressing a 660868-91-7 different mutant memTNF expressed as a transgene in mice deficient in both TNF and LTa . Only one study has been reported for M. tuberculosis infection using memTNFD112 KI mice showing protection to acute but not to chronic infection, and the infection dosage were lower than those used in the studies of memTNFD19,K11E KI mice . Infection with M. bovis BCG in memTNF KI mice has shown differential susceptibilities of these mice. MemTNFD19,K11E KI mice intranasally infected showed total resistance to M. bovis BCG infection, whereas memTNFD112 KI mice intravenously infected were only 50% resistant. The reasons PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/22190017 of differential susceptibility of the two memTNF KI mouse strains were not addressed in previous publications. To date, a rigorous comparison of immune responses elicited by intracellular bacterial infection in the two memTNF KI mice has not been performed and the importance of TNF receptors during a bacterial infection is unknown. To gain insights into the role of memTNF and its interaction with TNF receptors in protection against intracellular bacterial infection, we have compared resistance and cell-mediated immunity to M. bovis BCG infection of memTNFD19,K11E KI and memTNFD112 KI mice, and studied the pattern of cytokine and TNF receptor expression, and NF-kB activation. We used a systemic M. bovis BCG infection that allows these studies in highly sensitive mice such as TNF2/2 mice in which the pattern of inflammatory lesions have been well characterized. Considering that M. bovis BCG is the most widely distributed vaccination with live bacteria, deep investigation on the factors influencing protective immunity is still required. Our results show important differences between the two memTNF KI mouse strains in both resistance and cell-mediated immune responses to M. bovis BCG infection. 
These differences reveal distinct activities mediated by the interaction of either memTNFD19,K11E KI or memTNFD112 with TNF receptors. Our data show that cell-bound as well as soluble TNFR2 play a critical role in the outcome of the infection. Results Mice without solTNF and expressing only memTNFD1 9,K11E are more resistant to M. bovis BCG infection than mice with memTNFD112 To explore the protective activities of the transmembrane form of TNF against M. bovis BCG infection, we compared the development of host defense mechanisms against this pathogen in two different memTNF KI mouse strains. We infected wildtype, memTNFD19,K11E and memTNFD112, double TNFR1/TNFR22/2, and TNF2/2 mice by the i.v. route. Wild-type mice were resistant to M. bovis BCG infection; one out of 14 memTNFD19,K11E KI mice died, whereas 7 out of 10 memTNFD112 KI mice succumbed to the infection with loss of body weight, and all TNFR1/TNFR2 2/2 and TNF2/2 mice died. After i
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