The heterozygous mutant BiP mice grew up to be apparently normal adults. However, vulnerability to ER stress may exist in the mutant BiP mice, leading to chronic organ injuries. Indeed, some of them displayed motor disabilities in aging. We found a degeneration of some motoneurons in the spinal cord accompanied by accumulations of ubiquitinated proteins. The accumulation of misfolded proteins is one of the most common features in neurodegenerative diseases. Functional defects in the ER chaperones may contribute to the late onset of neurodegenerative diseases. Some of the mutant BiP mice revealed motor disabilities in aging. We found a degeneration of some motoneurons in the spinal cord accompanied by the accumulation of ubiquitinated proteins. BiP, also called the 78-kD glucose-regulated protein, is a member of the heat shock protein 70 family of proteins and is one of the most abundant ER chaperones, assisting in protein translocation, folding, and degradation.We speculate that the reduced parasite proliferation in the plate is due to high oxygen tension, which is deleterious to Giardia trophozoites. Together, these data suggest that our model is a better representation of giardiasis as parasites can reach higher densities in the insert environment and remain viable over many days. Indeed, the contradictory data on apoptosis during giardiasis is likely due to many factors including Giardia strain utilized, parasite density, and type of epithelial cell line used. The cytokine array illustrated the importance of co-culture in modulating cell phenotype. Caco-2 cells exhibit a different cytokine profile in the presence of human differentiated macrophages, which has been previously reported. Secretion of chemotatic cytokines, such as GRO isoforms and MCP-1, by intestinal epithelial cells incubated with Giardia has been reported. Our results partially supported our hypothesis, in that these effectors were mostly induced in planta.Studies in mice deficient in PD-1 or its ligands report increased numbers of Tfh cells, Cefetamet pivoxil HCl suggesting that PD-1/PD-L1 interactions downregulate Tfh generation and/or differentiation. While CTLA-4 is a potent inhibitor of effector T cell Euphorbia factor L3 differentiation and function, its role in regulating Tfh cell expansion is not known. Interestingly, our study reveals an important role for both PD-1 and CTLA-4 signaling in the down modulation of Tfh cell expansion in pulmonary TB since blockade of either of these pathways significantly restored the TB – antigen induced expansion of Tfh cell subsets in PTB individuals. These data provide novel insights into the role of PD-1 and CTLA-4 on the regulation of Tfh cells in a human infectio and suggest that imporant new roles for these molecules apart from their effect on T effector cells. In summary, our data on the Tfh cell distribution and function in pulmonary tuberculosis suggest that compromised Tfh cell numbers and function are a prominent feature of active disease. Although our study was not designed to decipher cause and effect mechanisms of Tfh association with active TB, it nevertheless implicates an important role for this poorly explored subset of CD4 T cells in active TB. Our study also provides the first comprehensive analysis of the distribution of B cell subsets in pulmonary TB and reveals that compromised B cell subset distribution is not a feature of active TB disease.