Activation of invariant NKT cells confers protection against Chlamydia trachomatis-induced arthritis

Bharhani, Mantej S.; Chiu, Brian; Na, Kyoung-Sun; Inman, Robert D.

doi:10.1093/intimm/dxp052

Cited by 16 publications

(17 citation statements)

References 35 publications

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“…CD1d-restricted NKT cells played a protective role in host defense against infection by some bacterial pathogens such as Mycobacterium tuberculosis and Pseudomonas aeruginosa [9,10], but the presence of these cells was detrimental in the case of Salmonella and Listeria infections [11,12]. In the case of chlamydial infections, CD1d-restricted NKT cells conferred protection against C. tracho-matis -induced arthritis [13], or C. muridarum -induced genital tract infection [14]; but Bilenki et al [15] have shown, conversely, that CD1d-restricted NKT cells promote C. muridarum lung infection. Moreover, using another chlamydial species, Chlamydophila pneumoniae , Joyee et al [16] reported that CD1d-restricted NKT cells play a crucial role in mediating the protective immune responses against lung infection.…”

Section: Introductionmentioning

confidence: 99%

CD1d-restricted NKT cells modulate placental and uterine leukocyte populations during chlamydial infection in mice

Habbeddine

Verbeke

Delarbre

et al. 2013

Microbes and Infection

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Invariant CD1d-restricted natural killer T cells play an important immunoregulatory role and can influence a broad spectrum of immunological responses including against bacterial infections. They are present at the fetal–maternal interface and although it has been reported that experimental systemic iNKT cell activation can induce mouse abortion, their role during pregnancy remain poorly understood. In the present work, using a physiological Chlamydia muridarum infection model, we have shown that, in vaginally infected pregnant mice, C. muridarum is cleared similarly in C57BL/6 wild type (WT) and CD1d−/− mice. We have also shown that infected- as well as uninfected-CD1d−/− mice have the same litter size as WT counterparts. Thus, CD1d-restricted cells are required neither for the resolution of chlamydial infection of the lower-genital tract, nor for the maintenance of reproductive capacity. However, unexpected differences in T cell populations were observed in uninfected pregnant females, as CD1d−/− placentas contained significantly higher percentages of CD4+ and CD8+ T cells than WT counterparts. However, infection triggered a significant decrease in the percentages of CD4+ T cells in CD1d−/− mice. In infected WT pregnant mice, the numbers of uterine CD4+ and CD8+ T cells, monocytes and granulocytes were greatly increased, changes not observed in infected CD1d−/− mice. An increase in the percentage of CD8+ T cells seems independent of CD1d-restricted cells as it occurred in both WT and CD1d−/− mice. Thus, in the steady state, the lack of CD1d-restricted NKT cells affects leukocyte populations only in the placenta. In Chlamydia-infected pregnant mice, the immune response against Chlamydia is dampened in the uterus. Our results suggest that CD1d-restricted NKT cells play a role in the recruitment or homeostasis of leukocyte populations at the maternal–fetal interface in the presence or absence of Chlamydia infection.

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Section: Introductionmentioning

confidence: 99%

CD1d-restricted NKT cells modulate placental and uterine leukocyte populations during chlamydial infection in mice

Habbeddine

Verbeke

Delarbre

et al. 2013

Microbes and Infection

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“…A similar Th1-biasing role for NKT cells involving DCs has been established in a murine infection model of Chlamydia pneumoniae [36]. Besides aiding Chlamydial clearance in mice, NKT cells have also been reported to have a protective role in Chlamydia trachomatis -induced arthritis [37]. CD1d −/− mice, which completely lack NKT cells, showed poor local bacterial clearance in the joint and more severe arthritis as compared to wild type controls.…”

Section: Bacterial Infectionsmentioning

confidence: 73%

Natural Killer T Cell Based Immunotherapy

Subrahmanyam

Sun²,

East³

et al. 2012

J Vaccines Vaccin

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Natural killer T (NKT) cells play an important immunoregulatory role and are thought to bridge the innate and adaptive immune responses. Following activation through cognate interactions with lipid antigen presented in the context of CD1d molecules, NKT cells rapidly produce a plethora of cytokines and can also mediate cytotoxicity. Due to their potent effector functions, extensive research has been performed to increase our understanding on how to effectively modulate these cells. In fact, NKT cell agonists have been used as vaccine adjuvants to enhance antigen specific T and B cell responses to infections and malignancy. In this review, we will focus on recent advances in NKT cell-based vaccination strategies. Given the role that NKT cells play in autoimmune disease, infectious diseases, cancer, transplant immunology and dermatology, it is important to understand how to effectively guide their effector functions in order to develop novel immunotherapeutic strategies.

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“…113 Additionally, in another infection-triggered form of arthritis, induced by Chlamydia trachomatis, iNKT cells are thought to have a protective role. 114 These studies suggest that iNKT cells have a non redundant role in regulating forms of infection-triggered arthritis and their extra-articular manifestations.…”

Section: Rheumatoid Arthritismentioning

confidence: 98%

Invariant natural killer T cells in rheumatic disease: a joint dilemma

2010

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Invariant natural killer T (iNKT) cells are an innate T-cell lineage known to recognize a range of endogenously derived and exogenously derived glycolipid antigens. Advances in our understanding of this T-cell subset have enabled researchers to investigate the immunomodulatory activity of iNKT cell ligands in experimental models of diseases such as cancer, allergy and chronic inflammatory joint disease. To a large extent, the ability of iNKT cells to regulate such disease models has been ascribed to their capacity to promote a polarized cytokine environment, which is understood to skew adaptive immune responses. In this Review, we discuss the current understanding of how iNKT-cell polarization is regulated and relate this basic theory to the proposed role for iNKT cells in models of rheumatologic disease.

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Activation of invariant NKT cells confers protection against Chlamydia trachomatis-induced arthritis

Cited by 16 publications

References 35 publications

CD1d-restricted NKT cells modulate placental and uterine leukocyte populations during chlamydial infection in mice

CD1d-restricted NKT cells modulate placental and uterine leukocyte populations during chlamydial infection in mice

Natural Killer T Cell Based Immunotherapy

Invariant natural killer T cells in rheumatic disease: a joint dilemma

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