Having said that, our knowing from the signalling pathways which are stimulated throughout mycobacterial infec tion and how the mycobacteria modulate these pathways is restricted. Latest scientific studies recommend that one feasible strat egy may possibly involve regulation and activation of protein tyrosine kinases that subsequently activate members of the STAT pathway, PI3K Akt pathway and mitogen activated protein kinase family members. MAP kinases really are a loved ones of serine threonine kinases that are activated by phosphorylation of conserved tyrosine residues. Several members of this relatives which include the p42 p44 extracellular signal regulated kinases, c Jun amino terminal kinases, and p38 MAP kinase have already been reported for being concerned in inflammatory mediator production in response to a wide selection of microbial stimuli.

For instance, ERK activation is concerned in response to Salmonella infection of macrophages, and MAP kinase activation is required for tumor necrosis selleck inhibitor element production in response to Group B strep tococcus infection. In addition, numerous labora tories have proven that MAP kinases are involved in macrophage activation following publicity to lipopolysac charide along with other bacterial cell wall elements. Current research have begun to investigate the purpose of these kinases in mycobacterial signalling. Early research by Chan et al showed the cell wall element of mycobacteria lipoarabinomannan stimu lated nitric oxide manufacturing via a pathway involving ERK and JNK. In addition, a variety of scientific studies have shown that infection of macrophages with intact myco bacteria activate certain MAP kinases.

Even further supporting a role for that significance of these selleck kinases in controlling microbial infection would be the findings that path ogenic strains of numerous bacteria block inflammatory mediator production through inhibition of MAP kinases. Following activation, MAP kinases phosphorylate particular transcription aspects resulting in modulation of cytokine gene transcription. A important transcription aspect concerned within the up regulation of several cytokines as well as other mediators necessary to host defense is nuclear factorB. Genes regulated by this aspect encode many professional teins involved within the early response to pathogens. Many groups have not too long ago reported activation of NF?B in response to both intact mycobacteria and mycobacterial cell wall elements, and NF?B activation is reported in monocytes of individuals infected with M.

tuberculosis. Our laboratory has been studying the position that host things play in improving the innate response to challenge by invading mycobacteria. Considered one of these variables is surfactant associated protein A, a member in the C variety lectin loved ones which is synthesized and secreted by kind II epithelial cells while in the lung. Operate from many laboratories has demonstrated that SP A plays a significant purpose during the clear ance of the variety of respiratory pathogens throughout the innate host response. In vitro research have proven that SP A functions as an opsonin and enhances the ingestion of this kind of pathogens as BCG, Mycobacterium tuberculosis, influenza A virus,E. coli, Haemophilus influ enzae, Staphylococcus aureus, Streptococcus pneu moniae, Mycoplasma pulmonis and Klebsiella pneumoniae.

The importance of SP A in in vivo host defense is supported lately through the demonstra tion that mice deficient in SP A show decreased resistance to group B streptococcal and Pseudomonas aeruginosa pneumonia, decreased clearance of respiratory syncytial virus, and lowered killing of mycoplasma. In in vitro scientific studies, Kabha et al. and Hickman Davis et al. demonstrated that SP A enhances the ingestion and killing of K. pneumoniae and mycoplasma by macrophages. Recent function from our laboratory has shown that SP A enhances clearance of BCG and avirulent Mycobacterium tuberculosis by cultured rat macrophages. This enhanced clearance is accompanied by enhanced professional duction of nitric oxide and TNF.