Precarious Balance: Th17 Cells in Host Defense

Department of Pediatrics, Division of Immunology and Transplantation Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Infection and immunity (Impact Factor: 3.73). 11/2009; 78(1):32-8. DOI: 10.1128/IAI.00929-09
Source: PubMed


Lineage-specific responses from the effector T-cell repertoire form a critical component of adaptive immunity. The recent
identification of Th17 cells—a third, distinct lineage of helper T cells—collapses the long-accepted paradigm in which Th1
and Th2 cells distinctly mediate cellular and humoral immunity, respectively. In this minireview, we discuss the involvement
of the Th17 lineage during infection by extracellular bacteria, intracellular bacteria, and fungi. Emerging trends suggest
that the Th17 population bridges innate and adaptive immunity to produce a robust antimicrobial inflammatory response. However,
because Th17 cells mediate both host defense and pathological inflammation, elucidation of mechanisms that attenuate but do
not completely abolish the Th17 response may have powerful implications for therapy.

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Available from: Elizabeth Mellins, Dec 17, 2013
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    • "TLR5 stimulation, responding to bacterial flagellin, can additionally contribute to acute inflammation during UTI[11,12]. Perpetuation of the neutrophil response may be driven by cytokines such as IL-17, which has an emerging role in bridging innate to adaptive immunity[13]and is a mediator of the innate response during experimental UTI[14]. The human cathelicidin LL-37, a small, cationic antibacterial peptide, is detectable in the urine during human cystitis, and mice deficient in its ortholog (CRAMP) demonstrate increased susceptibility to pyelonephritis[15], although it may paradoxically enhance bladder infection[16]. "
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    ABSTRACT: Uropathogenic Escherichia coli (UPEC) cause the majority of community-onset urinary tract infections (UTI) and represent a major etiologic agent of healthcare-associated UTI. Introduction of UPEC into the mammalian urinary tract evokes a well-described inflammatory response, comprising pro-inflammatory cytokines and chemokines as well as cellular elements (neutrophils and macrophages). In human UTI, this inflammatory response contributes to symptomatology and provides means for diagnosis by standard clinical testing. Early in acute cystitis, as demonstrated in murine models, UPEC gains access to an intracellular niche that protects a population of replicating bacteria from arriving phagocytes. To ensure the establishment of this protected niche, UPEC employ multiple strategies to attenuate and delay the initiation of host inflammatory components, including epithelial secretion of chemoattractants. Recent work has also revealed novel mechanisms by which UPEC blunts neutrophil migration across infected uroepithelium. Taken together, these attributes distinguish UPEC from commensal and nonpathogenic E. coli strains. This review highlights the unique immune evasion and suppression strategies of this bacterial pathogen and offers directions for further study; molecular understanding of these mechanisms will inform the development of adjunctive, anti-virulence therapeutics for UTI.
    Full-text · Article · Jan 2016 · Pathogens
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    • "Because of the discovery of an IL-17-producing T-cell subset, known as Th17, numerous studies have revealed IL-17 as a pro-inflammatory cytokine involved in the pathogenesis of autoimmune disorders as well as in response to certain pathogens at both the barrier site and at a systemic level (O'Connor et al., 2010; Miossec and Kolls, 2012). Th17 cells have a role in the protection against extracellular bacteria and fungi (Zhu and Paul, 2008; Zhu et al., 2010), particularly those colonizing the respiratory and gastrointestinal tracts and the skin (Peck and Mellins, 2010). The protective effects of IL-17-producing cells have been demonstrated in patients with hyper-immunoglobulin E syndrome, who suffer from recurrent infections with Candida albicans (C. "
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    ABSTRACT: Propionibacterium acnes is a Gram-positive commensal bacterium thought to be involved in the pathogenesis of acne vulgaris. While the ability of P. acnes in the initiation of pro-inflammatory responses is well documented, little is known about adaptive immune responses to this bacterium. The observation that infiltrating immune cells consist mainly of CD4(+) T cells in the perifollicular space of early acne lesions suggests that helper T cells may be involved in immune responses caused by the intra-follicular colonization of P. acnes. A recent report showing that P. acnes can induce IL-17 production by T cells suggests that acne might be a Th17-mediated disease. In line with this, we show in this work that, in addition to IL-17 A both Th1 and Th17 effector cytokines, transcription factors and chemokine receptors are strongly upregulated in acne lesions. Furthermore, we found that, in addition to Th17, P. acnes can promote mixed Th17/Th1 responses by inducing the concomitant secretion of IL-17 A and IFNγ from specific CD4(+) T cells in vitro. Finally, we show that both P. acnes-specific Th17 and Th17/Th1 cells can be found in the peripheral blood of patients suffering from acne and, at lower frequencies, in healthy individuals. We therefore identified P. acnes-responding Th17/Th1 cells as previously unreported CD4(+) sub-population involved in inflammatory acne.Journal of Investigative Dermatology accepted article preview online, 10 July 2014; doi:10.1038/jid.2014.290.
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    • "By contrast, the roles of adaptive immune cells in the generation of protective anti-cryptococcal infection immune responses have been widely accepted. Studies have shown that increased IL-17A production, a pro-inflammatory cytokine which is predominantly secreted by CD4+ T cells, is associated with cryptococcal burden (5,7). Furthermore, IL-17A secreted by CD4+ T helper (Th)17 cells is involved in multiple roles as a ‘bridge’ that is associated with innate and adaptive immune responses. "
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    ABSTRACT: Cryptococcosis is a potentially fatal fungal disease commonly identified in patients with acquired immunodeficiency syndrome. Cryptococcus infection induces strong pro-inflammatory cytokine secretion, i.e. type-I interferon (IFN-I) via the Toll-like receptor signaling pathway. However, innate immune responses are insufficient in host defense against fungi infection and the clearance of Cryptococcus is dependent on the T helper (Th)17 cell-mediated mucosal immune response. In this study, IFN-I was identified as the early response cytokine to Cryptococcus neoformans infection via quantitative PCR (qPCR) and IFN-I was demonstrated to be crucial for interleukin (IL)-17A secretion in T cells, but not in innate immune cells. In addition, blockade of IFN-I reduced the protein expression levels of IL-22 and IL-23 in Th17 cells in vitro. These results suggest additional functions of IFN-I in immune regulation, which may be pivotal for the development of clinical immune therapy.
    Full-text · Article · Apr 2014 · Experimental and therapeutic medicine
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