Host control of mycobacterial or helminth infections largely rely on the induction of appropriately polarized immune responses. Protective immune responses to M. tb infection are associated with enhanced T helper 1 (TH1) type cellular immunity and the production of characteristic TH1 cytokines such as buy LY3023414 tumor

necrosis factor alpha (TNF-α), interferon-gamma (IFN-γ) and interleukin-12 (IL-12) [8]. Conversely, protection against most helminths requires a T helper 2 (TH2) type cellular immune response with production of distinct TH2 cytokines such as IL-4, IL-5, IL-13 and IL-9 [9, 10]. Since TH1 and TH2 immune responses have the ability to concurrently down-regulate each other, a state of co-infection could result in inappropriate

protective host immune responses to either infections [11]. Furthermore, both pathogens have the potential to induce regulatory BI 2536 ic50 T cell (Treg) responses associated with production of immune suppressive cytokines such as IL-10 and transforming growth factor beta (TGF-β) [10–13]. In line with the TH1/TH2 dichotomy, hypotheses concerning helminth-mycobacterial co-infection postulate that a helminth-induced TH2 immune bias could inhibit development of protective cellular immune responses to M. tb, increase mycobacterial proliferation or lead to the failure of vaccine strategies against TB [14, 15]. This theory is supported by numerous studies which have Torin 1 price reported a reduction in TH1 responses to be associated fantofarone with poor outcomes in TB patients [16] and latently infected individuals [17] with concurrent helminth infection. Helminth-induced regulatory (Treg) responses such as TGF-β and IL-10 production have also been implicated in S. mansoni-induced progression to active

TB of HIV-1 infected Ugandans [18]. It was also established that deworming of helminth-infected individuals restores cellular immune responses to mycobacterial purified protein derivatives (PPD) [19–21]. Similarly, deworming of helminth-infected Ethiopians immigrants in Israel resulted in increased cellular immune responses against HIV- and M. tb-specific antigens compared to untreated individuals [22], suggesting deteriorating immune responses and poor clinical outcomes in helminth-infected individuals might not be a result of inadequate nutrition or sanitation. Several reports have also indicated helminth-mediated modulation of vaccine responses. Children with prenatal sensitization to filariae and schistosomes were reported to display a down-regulation in TH1 responsiveness to BCG vaccination [23] and animal co-infection models have further demonstrated that a pre-existing infection with a lung-migrating helminth, can inhibit development of protective innate anti-TB responses by inducing the IL-4 receptor pathway and accumulation of alternatively activated macrophages [24].