Precarious Balance: Th17 Cells in Host Defense

Peck, Ariana; Mellins, Elizabeth

doi:10.1128/iai.00929-09

Cited by 192 publications

(164 citation statements)

References 106 publications

(139 reference statements)

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“…Recently, the inflammatory response to N. gonorrhoeae was shown to occur through the Th17 pathway in the female mouse model of gonococcal infection (8). This finding is consistent with the detection of Th17 responses in humans with gonorrhea (9) and the central role that the Th17 pathway plays in infections by other pyogenic cocci (10). Differentiation and proliferation of Th17 cells occur under the influence of the interleukin 6 (IL-6), transforming growth factor ␤ (TGF-␤), IL-1␤, and IL-23 produced by antigenpresenting cells in response to microbial stimulation.…”

supporting

confidence: 78%

Phosphoethanolamine Decoration of Neisseria gonorrhoeae Lipid A Plays a Dual Immunostimulatory and Protective Role during Experimental Genital Tract Infection

et al. 2014

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eThe induction of an intense inflammatory response by Neisseria gonorrhoeae and the persistence of this pathogen in the presence of innate effectors is a fascinating aspect of gonorrhea. Phosphoethanolamine (PEA) decoration of lipid A increases gonococcal resistance to complement-mediated bacteriolysis and cationic antimicrobial peptides (CAMPs), and recently we reported that wild-type N. gonorrhoeae strain FA1090 has a survival advantage relative to a PEA transferase A (lptA) mutant in the human urethral-challenge and murine lower genital tract infection models. Here we tested the immunostimulatory role of this lipid A modification. Purified lipooligosaccharide (LOS) containing lipid A devoid of the PEA modification and an lptA mutant of strain FA19 induced significantly lower levels of NF-B in human embryonic kidney Toll-like receptor 4 (TLR4) cells and murine embryonic fibroblasts than wild-type LOS of the parent strain. Moreover, vaginal proinflammatory cytokines and chemokines were not elevated in female mice infected with the isogenic lptA mutant, in contrast to mice infected with the wild-type and complemented lptA mutant bacteria. We also demonstrated that lptA mutant bacteria were more susceptible to human and murine cathelicidins due to increased binding by these peptides and that the differential induction of NF-B by wild-type and unmodified lipid A was more pronounced in the presence of CAMPs. This work demonstrates that PEA decoration of lipid A plays both protective and immunostimulatory roles and that host-derived CAMPs may further reduce the capacity of PEA-deficient lipid A to interact with TLR4 during infection.

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supporting

confidence: 78%

Phosphoethanolamine Decoration of Neisseria gonorrhoeae Lipid A Plays a Dual Immunostimulatory and Protective Role during Experimental Genital Tract Infection

et al. 2014

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“…Th1/Th17 cells have recently been described (35). Although the host defense against extracellular bacteria is widely considered pertaining to the Th17 arm, some evidence indicates that efficient protection requires synergy between the Th1 and Th17 lineages (36,37). Whether these double-positive cells represent a subset of cells in a transient stage of Th development or a new population derived from a distinct but unknown differentiation program remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Attenuated Bordetella pertussis Vaccine Candidate BPZE1 Promotes Human Dendritic Cell CCL21-Induced Migration and Drives a Th1/Th17 Response

Fedele

Bianco

Debrie

et al. 2011

The Journal of Immunology

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New vaccines against pertussis are needed to evoke full protection and long-lasting immunological memory starting from the first administration in neonates—the major target of the life-threatening pertussis infection. A novel live attenuated Bordetella pertussis vaccine strain, BPZE1, has been developed by eliminating or detoxifying three important B. pertussis virulence factors: pertussis toxin, dermonecrotic toxin, and tracheal cytotoxin. We used a human preclinical ex vivo model based on monocyte-derived dendritic cells (MDDCs) to evaluate BPZE1 immunogenicity. We studied the effects of BPZE1 on MDDC functions, focusing on the impact of Bordetella-primed dendritic cells in the regulation of Th and suppressor T cells (Ts). BPZE1 is able to activate human MDDCs and to promote the production of a broad spectrum of proinflammatory and regulatory cytokines. Moreover, conversely to its parental wild-type counterpart BPSM, BPZE1-primed MDDCs very efficiently migrate in vitro in response to the lymphatic chemokine CCL21, due to the inactivation of pertussis toxin enzymatic activity. BPZE1-primed MDDCs drove a mixed Th1/Th17 polarization and also induced functional Ts. Experiments performed in a Transwell system showed that cell contact rather than the production of soluble factors was required for suppression activity. Overall, our findings support the potential of BPZE1 as a novel live attenuated pertussis vaccine, as BPZE1-challenged dendritic cells might migrate from the site of infection to the lymph nodes, prime Th cells, mount an adaptive immune response, and orchestrate Th1/Th17 and Ts responses.

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“…Th17 responses are known to enhance antimicrobial inflammatory responses by increasing the expression of antimicrobial peptides and effectively recruiting and activating neutrophils that contribute to destroying invading extracellular pathogens. 84,85 Notably, EAEC clearance was directly correlated with the upregulation of colonic calprotectin in GW9662 treated mice. The beneficial role of Th17 cells to enhance effector mucosal responses during EAEC infections is a pivotal finding and future studies should focus on how EAEC induces these responses.…”

mentioning

confidence: 99%