IL-17 has been implicated in many inflammatory diseases, including rheumatoid arthritis, multiple sclerosis, asthma and systemic lupus erythematosus [12–14]. The role of Th17 cytokines in tuberculosis has recently been investigated. Proteasome inhibitor IL-17 plays a key role in early neutrophil-mediated pulmonary inflammatory responses, T cell-mediated IFN-γ production and granuloma formation in the lung in response to infection with bacillus Calmette–Guérin (BCG) [15,16]. Studies in IL-23- and IL-12/23-deficient mice have highlighted the importance of the role played by the IL-23/Th17 pathway in immune responses against mycobacterial infection [2,17]. Furthermore, IL-17 accelerates memory Th1 responses in vaccinated mice infected

subsequently with Mycobacterium tuberculosis[15]. IL-22, a member of the IL-10 family of cytokines, is also produced by Th17 cells [13,18]. It acts primarily on non-immune BMN 673 price cells, as IL-22R is not expressed on immune cells [19]. IL-22 plays a protective role during inflammation of various tissues, including liver, intestine and heart [20–22], perhaps by inducing the release of anti-microbial agents such as β-defensin-2 and proinflammatory molecules belonging to the S100 family of calcium-binding proteins [18]. In contrast to IL-17, the role of IL-22 in tuberculosis is not well defined; however, in patients with active tuberculosis (TB), elevated levels of IL-22

in bronchoalveolar lavage specimens have been reported [23]. IL-17 has also been shown to mobilize, recruit and activate neutrophils [24] which appear early during mycobacterial infection. The role of granulocytes in tuberculosis is not clear, but reports suggest that they release chemokines to recruit monocytes and contribute to granuloma formation [25,26]. The lack of neutrophils during the early stages of infection increases bacterial burden in infected tissues because of decreased production of TNF-α, Tobramycin IL-1 and IL-12 [27]. Moreover, neutrophils directly affect mycobacterial killing activity by releasing anti-microbial peptides such as cathelicidin LL-37

and lipocalin-2 [28]. In addition to a protective response, neutrophils may be involved in the destructive immune responses in active tuberculosis [29,30]. Mice infected with the virulent strains of M. tuberculosis exhibited formation of granulomas with lymphopenic and granulocytic lesions which resulted ultimately in the death of the host [29]. Furthermore, IL-27-deficient mice infected with mycobacteria succumbed to death due to hyperinflammatory responses when granulomatous lesions have abundant neutrophils [30]. To gain insight into the involvement of Th17 cells, we measured basal levels of IL-17/IL-22 expressing lymphocytes and granulocytes and secretion of proinflammatory cytokines including IL-17 and IL-22 in circulation as well as following peripheral blood mononuclear cell (PBMC) stimulation with mycobacterial antigens in individuals with both latent and active stages of disease.