T helper Th cells play

T helper (Th) concentration calculation play a central role in activation of immune system against infectious agents through secretion of lymphokines or cytokines. African trypanosomes target the Th cells and alter their activation, possibly for their own survival and perpetuity (Namangala, 2011). Trypanosoma brucei impairs both IL-2 production and IL-2 receptor expression by T cells and thereby depression of T-cell proliferative response in mice. Lymphocytes possess cholinergic components necessary to constitute an independent, non-neuronal cholinergic system (Fujii et al., 2008) and this lymphocytic cholinergic system could play a key role in modulation of immune functions via both muscarinic and nicotinic cholinergic receptors. In most trypanosome infection models, a strong Th1 protective response, mainly during early trypanosomosis has been reported (Mansfield and Paulnock, 2005, Namangala et al., 2009). Trypanosomes may evade such immune responses by inducing irrelevant immune responses during early stages of infection through enhancement of Th2 cytokines production and regulatory T-cell activation which results in increased production of IL-10 and TGF-β, both of which suppress early protective Th1 responses and hence favour parasite survival (Hertz et al., 1998, Tabel et al., 2008). Therefore, it is quite possible that T. evansi might be utilizing vagal cholinergic pathway to impair Th1 immune response or to enhance Th2 anti-inflammatory response in infected buffaloes possibly for their own survival and perpetuity. Mechanism of neurological signs in trypanosomosis is obscure. Recently, studies on experimental infections with T. evansi in various experimental animals have revealed remarkable reduction in cholinesterase activity (Da Silva et al., 2010, Da Silva et al., 2011b, Wolkmer et al., 2010, Wolkmer et al., 2013). In the present study too, significant difference in cholinesterase activity was observed between T. evansi-infected and healthy buffaloes; thereby suggesting direct correlation between T. evansi infection and cholinesterase activity. But, cholinesterase activity was not found to be associated with neurological disorders as significant inhibition of cholinesterase was observed even in those clinical cases which did not exhibit any neurological signs. Neurological signs might be the consequence of necrotizing panencephalitis or meningoencephalitis (Rodrigues et al., 2009), ordue to alterations in actions of neurotransmitters (Da Silva et al., 2011a, Paim et al., 2011). Reduced cholinesterase activity in buffaloes in the present study is in agreement with the scientific reports demonstrating reduction in cholinesterase activity in T. evansi infected animals (Da Silva et al., 2010, Wolkmer et al., 2010). But are just contrary to the observations of Costa et al. (2012) who have reported remarkable increase in cholinesterase activity in blood of experimentally T. evansi infected rabbits on days 7 and 27 post-infection. These differences could be due to species difference between buffaloes and rabbits as the clinical signs and severity of disease is also different in buffaloes and rabbits as amongst the affected mammalian species, camels, horses, buffaloes and dogs have the most severe form of disease (Taylor and Authié, 2004). In conclusion, significantly reduced cholinesterase activity seems to be associated with pathogenesis of natural T. evansi infection and its clinical manifestations in buffaloes probably by evading immune response for their own survival and perpetuity. But based on this study, it is not possible to suggest the possible mechanism of cholinesterase inhibition and its association with neurological manifestations in buffaloes except for possible release of some endogenous mediator (s) or alterations in activity of neurotransmitters (Da Silva et al., 2011a, Paim et al., 2011) which may be responsible for neurological or non-neurological disorders. Further, possibility of promising therapeutic potential of cholinesterase reactivators in management of trypanosomosis in buffaloes and other species cannot be ruled out, but requires further studies.