IL-12p40 and IL-18 Play Pivotal Roles in Orchestrating the Cell-Mediated Immune Response to a Poxvirus Infection

Wang, Yang; Chaudhri, Geeta; Jackson, Ron; Karupiah, Gunasegaran

doi:10.4049/jimmunol.0803985

Cited by 51 publications

(75 citation statements)

References 57 publications

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“…IL-12, a proinflammatory cytokine, was also produced rapidly by monocytes in ,2 h after interactions with CHIKV. Although this cytokine has no direct antiviral role, it is known to activate NK cells to increase antiviral activities (48,49). IFN-a that was also produced by monocytes alone or in whole blood cultures postinfection at later time points (24-48 h), have also been shown to possess similar activities on NK cells (50).…”

Section: Discussionmentioning

confidence: 99%

Active Infection of Human Blood Monocytes by Chikungunya Virus Triggers an Innate Immune Response

Her

Malleret

Chan

et al. 2010

The Journal of Immunology

253

254

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Chikungunya virus (CHIKV) is an alphavirus that causes chronic and incapacitating arthralgia in humans. To date, interactions between the immune system and the different stages of the virus life cycle remain poorly defined. We demonstrated for the first time that CHIKV Ags could be detected in vivo in the monocytes of acutely infected patients. Using in vitro experimental systems, whole blood and purified monocytes, we confirmed that monocytes could be infected and virus growth could be sustained. CHIKV interactions with monocytes, and with other blood leukocytes, induced a robust and rapid innate immune response with the production of specific chemokines and cytokines. In particular, high levels of IFN-α were produced rapidly after CHIKV incubation with monocytes. The identification of monocytes during the early phase of CHIKV infection in vivo is significant as infected monocyte/macrophage cells have been detected in the synovial tissues of chronically CHIKV-infected patients, and these cells may behave as the vehicles for virus dissemination. This may explain the persistence of joint symptoms despite the short duration of viremia. Our results provide a better understanding on the basic mechanisms of infection and early antiviral immune responses and will help in the development of future effective control strategies.

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Section: Discussionmentioning

confidence: 99%

Active Infection of Human Blood Monocytes by Chikungunya Virus Triggers an Innate Immune Response

Her

Malleret

Chan

et al. 2010

The Journal of Immunology

253

254

View full text Add to dashboard Cite

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“…Absence of both IL-12p40 and IL-18 resulted in increased susceptibility to infection and reduction in NK and CTL responses. IL-12p40 and IL-18 act in concert and play an important antiviral role through the up-regulation of IFNgamma production and cell-mediated immune responses (Wang et al, 2009). Post transplant lympho proliferative disease tissues express significantly lower levels of IL-18 and interferon-gamma permitting the uncontrolled expansion of Epstein-Barr virus (EBV)-infected B lymphocytes, compared to lymphoid tissues diagnosed with acute EBV-induced infectious mononucleosis (Setsuda et al, 1999).…”

Section: Role Of Il-18 In Immune Evasuionmentioning

confidence: 99%

Immunotherapeutic Approach for Better Management of Cancer - Role of IL-18

Kuppala¹,

Syed²,

Bandaru³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Interleukin-18 (IL-18) is an immune-stimulatory cytokine with antitumor activity in preclinical models. It plays pivotal roles in linking inflammatory immune responses and tumor progression and is a useful candidate in gene therapy of lymphoma or lymphoid leukemia. A phase I study of recombinant human IL-18 (rhIL-18) in patients with advanced cancer concluded that rhIL-18 can be safely given in biologically active doses to patients with advanced cancer. Some viruses can induce the secretion of IL-18 for immune evasion. The individual cytokine activity might be potentiated or inhibited by combinations of cytokines. Here we focus on combinational effects of cytokines with IL-18 in cancer progression. IL-18 is an important non-invasive marker suspected of contributing to metastasis. Serum IL-18 may a useful biological marker as independent prognostic factor of survival. In this review we cover roles of IL-18 in immune evasion, metastasis and angiogenesis, applications for chemotherapy and prognostic or diagnostic significance.

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“…For example, because SCS macrophages are preferentially infected following VV and CPXV infection, the lack of this population in clodronate-loaded, liposome-treated mice may lead to a lack of pathogen sensing, via pattern recognition receptors or nuclei acid sensors, for example, which would otherwise induce production of other mediators that affect NK-cell recruitment. These mediators could include other chemokines that are initially required, such as the ligands for CCR2/5, or proinflammatory factors, such as IL-12 and IL-18 (65). However, CPXV encodes an IL-18 binding protein that binds with high affinity to murine IL-18, which could potentially inhibit stimulation of SCS macrophages; thus, it is possible that SCS macrophage stimulation may occur through an alternate pathway (41,65).…”

mentioning

confidence: 99%

“…These mediators could include other chemokines that are initially required, such as the ligands for CCR2/5, or proinflammatory factors, such as IL-12 and IL-18 (65). However, CPXV encodes an IL-18 binding protein that binds with high affinity to murine IL-18, which could potentially inhibit stimulation of SCS macrophages; thus, it is possible that SCS macrophage stimulation may occur through an alternate pathway (41,65). All together, these results suggest that although macrophages play an important role following both parasitic and viral infection, their precise role in poxvirus infection will require further investigation.…”

mentioning

confidence: 99%

Interferon-γ mediates chemokine-dependent recruitment of natural killer cells during viral infection

Pak-Wittel¹,

Yang²,

Sojka³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Natural killer (NK) cells provide in vivo control of orthopoxvirus infections in association with their expansion in the draining lymph node (LN), where they are normally very rare. The mechanism of this expansion is unclear. Herein, we determined that NK-cell depletion results in enhanced infection following footpad inoculation of cowpox virus, a natural pathogen of rodents. Following cowpox virus infection in normal mice, NK cells were greatly expanded in the draining LN, were not replicating, and displayed markers similar to splenic NK cells, suggesting specific recruitment of splenic NK cells rather than in situ proliferation. Moreover, NK-cell expansion was abrogated by prior injection of clodronate-loaded liposomes, indicating a role for subcapsular sinus macrophages. Furthermore, recruitment of transferred splenic NK cells to the draining LN was pertussis toxin-sensitive, suggesting involvement of chemokine receptors. Comprehensive analysis of chemokine mRNA expression in the draining LN following infection suggested the selective involvement of CCR2, CCR5, and/or CXCR3. Mice deficient for CCR2 or CCR5 had normal NK-cell recruitment, whereas CXCR3-deficient mice displayed a major defect, which was NK cell-intrinsic. Interestingly, both induction of transcripts for CXCR3 ligands (Cxcl9 and Cxcl10) and NK-cell recruitment required IFN-γ. These data indicate that NK-cell recruitment is mediated by subcapsular sinus macrophages, IFN-γ, and CXCR3 during orthopoxvirus infection.

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IL-12p40 and IL-18 Play Pivotal Roles in Orchestrating the Cell-Mediated Immune Response to a Poxvirus Infection

Cited by 51 publications

References 57 publications

Active Infection of Human Blood Monocytes by Chikungunya Virus Triggers an Innate Immune Response

Active Infection of Human Blood Monocytes by Chikungunya Virus Triggers an Innate Immune Response

Immunotherapeutic Approach for Better Management of Cancer - Role of IL-18

Interferon-γ mediates chemokine-dependent recruitment of natural killer cells during viral infection

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