NK Cells Enhance Dendritic Cell Response against Parasite Antigens via NKG2D Pathway

Guan, Hongbing; Moretto, Magali; Bzik, David J.; Gigley, Jason P.; Khan, Imtiaz Ali

doi:10.4049/jimmunol.179.1.590

Cited by 68 publications

(60 citation statements)

References 43 publications

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“…Although the mechanisms or molecules involved in this DC-NK cell cross talk remain unclear, previous reports have suggested the participation of NKG2D in DC-NK cell responses to Toxoplasma gondii antigens (20) and the involvement of proteins of high-mobility group I in DC-ANK cell interaction (36). Another important finding in the present study is that while infection with L. amazonensis promastigotes …”

Section: Discussionsupporting

confidence: 65%

Role of Natural Killer Cells in Modulating Dendritic Cell Responses toLeishmania amazonensisInfection

Sanabria¹,

Vargas-Inchaustegui²,

Luo³

et al. 2008

Infect Immun

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The importance of the interaction between natural killer (NK) cells and dendritic cells (DCs) in the expansion of antiviral and antitumor immune responses is well-documented; however, limited information on DC-NK cell interaction during parasitic infections is available. Given that some Leishmania parasites are known to prevent or suppress DC activation, we developed a DC-NK cell coculture system to examine the role of NK cells in modulating the functions of Leishmania-infected DCs. We found that the addition of freshly isolated, resting NK cells significantly promoted the activation of DCs that were preinfected with Leishmania amazonensis promastigotes and that these activated DCs, in turn, stimulated NK cell activation mostly via cell contact-dependent mechanisms. Notably, L. amazonensis amastigote infection failed to activate DCs, and this lack of DC activation could be partially reversed by the addition of preactivated NK (ANK) cells but not resting NK cells. Moreover, the adoptive transfer of ANK cells into L. amazonensis-infected mice markedly increased DC and T-cell activation and reduced tissue parasite loads at 1 and 3 weeks postinfection. These results suggest differential roles of DC-NK cell cross talk at different stages of Leishmania infection and provide new insight into the interplay of components of the innate immune system during parasitic infection.

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Section: Discussionsupporting

confidence: 65%

Role of Natural Killer Cells in Modulating Dendritic Cell Responses toLeishmania amazonensisInfection

Sanabria¹,

Vargas-Inchaustegui²,

Luo³

et al. 2008

Infect Immun

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show abstract

“…Some recent studies have addressed the mechanisms by which NK cell might interact with DC (41)(42)(43). A recent study showed that NK cells can enhance the capacity of DC to present parasitic Ags via NKG2D receptor pathway (44). Using the NK-DC coculture approach, we demonstrated the direct influence of NK cells on DC FIGURE 8.…”

Section: Discussionmentioning

confidence: 99%

NK Cells Promote Type 1 T Cell Immunity through Modulating the Function of Dendritic Cells during Intracellular Bacterial Infection

Jiao

Gao

Joyee

et al. 2011

The Journal of Immunology

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Dendritic cells (DC) play a key role in establishing protective adaptive immunity in intracellular bacterial infections, but the cells influencing DC function in vivo remain unclear. In this study, we investigated the role of NK cells in modulating the function of DC using a murine Chlamydia infection model. We found that the NK cell-depleted mice showed exacerbated disease after respiratory tract Chlamydia muridarum infection, which was correlated with altered T cell cytokine profile. Furthermore, DC from C. muridarum-infected NK-depleted mice (NK−DC) exhibited a less mature phenotype compared with that of DC from the infected mice without NK depletion (NK+DC). NK−DC produced significantly lower levels of both IL-12 and IL-10 than those of NK+DC. Moreover, NK−DC showed reduced ability to direct primary and established Ag-specific Th1 CD4+ T cell responses in DC–T coculture systems. More importantly, adoptive transfer of NK−DC, in contrast to NK+DC, failed to induce type 1 protective immunity in recipients after challenge infection. Finally, NK cells showed strong direct enhancing effect on IL-12 production by DC in an NK–DC coculture system, which was partially reduced by blocking NKG2D receptors signaling and virtually abolished by neutralizing IFN-γ activity. The data demonstrate a critical role of NK cells in modulating DC function in an intracellular bacterial infection.

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“…Moreover, a previously unappreciated role for NKG2D and its ligands in nonclassical NK T-cell-mediated immune responses has been revealed by using a transgenic mouse model of human hepatitis B infection (89). In addition, NKG2D-mediated interactions between NK cells and professional antigen-presenting cells have been shown to lead to stronger priming of antigen-specific CD8 ϩ T-cell responses by increasing interleukin-12 (IL-12) production from dendritic cells containing an antigen from Toxoplasma gondii lysate (36). Treatment of T. gondii-infected mice with anti-NKG2D antibody impaired the development of antigen-specific CD8 ϩ T cells, which led to a reduced ability to clear parasites from infected tissues.…”

Section: Discussionmentioning

confidence: 99%

NKG2D Receptor Signaling Enhances Cytolytic Activity by Virus-Specific CD8⁺T Cells: Evidence for a Protective Role in Virus-Induced Encephalitis

Walsh

Lanier

Lane

2008

J Virol

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Inoculation with the neurotropic JHM strain of mouse hepatitis virus (JHMV) into the central nervous system (CNS) of mice results in an acute encephalitis associated with an immune-mediated demyelinating disease. During acute disease, infiltrating CD8 ؉ T cells secrete gamma interferon (IFN-␥) that controls replication in oligodendrocytes, while infected astrocytes and microglia are susceptible to perforin-mediated lysis. The present study was undertaken to reveal the functional contributions of the activating NKG2D receptor in host defense and disease following JHMV infection. NKG2D ligands RAE-1, MULT1, and H60 were expressed within the CNS following JHMV infection. The immunophenotyping of infiltrating cells revealed that NKG2D was expressed on ϳ90% of infiltrating CD8 ؉ T cells during acute and chronic disease. Blocking NKG2D following JHMV infection resulted in increased mortality that correlated with increased viral titers within the CNS. Anti-NKG2D treatment did not alter T-cell infiltration into the CNS or the generation of virus-specific CD8 ؉ T cells, and the expression of IFN-␥ was not affected. However, cytotoxic T-lymphocyte (CTL) activity was dependent on NKG2D expression, because anti-NKG2D treatment resulted in a dramatic reduction in lytic activity by virus-specific CD8 ؉ T cells. Blocking NKG2D during chronic disease did not affect either T-cell or macrophage infiltration or the severity of demyelination, indicating that NKG2D does not contribute to virus-induced demyelination. These findings demonstrate a functional role for NKG2D in host defense during acute viral encephalitis by selectively enhancing CTL activity by infiltrating virus-specific CD8 ؉ T cells.Viral infection of the central nervous system (CNS) presents unique challenges to the immune system with regard to controlling and eliminating the invading pathogen. These obstacles include the presence of a blood-brain barrier that provides a physical and physiological barrier that is difficult for cells and molecules to cross, the absence of classic lymphatic drainage that may impair the generation of an adaptive immune response, and the relative absence of major histocompatibility complex (MHC) class I or II expression on resident cells (3,26,39,73). In addition, the CNS is composed of a variety of highly specialized cells, many of which have limited renewal capacity, that represent potential targets of infection by numerous different viruses (34, 81). Therefore, a significant hurdle encountered by infiltrating antigen-specific lymphocytes is the elimination of virus from infected cells while limiting the damage that may have long-term detrimental consequences to the host. Critical to this is the cellular tropism of the virus, as this is important in dictating the effector response by infiltrating lymphocytes. For example, neuronotropic viruses often are eliminated by noncytolytic mechanisms via cytokine-mediated control and/or neutralizing antibodies, whereas the infection of other cell populations can evoke cytolytic mechanisms for c...

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NK Cells Enhance Dendritic Cell Response against Parasite Antigens via NKG2D Pathway

Cited by 68 publications

References 43 publications

Role of Natural Killer Cells in Modulating Dendritic Cell Responses toLeishmania amazonensisInfection

Role of Natural Killer Cells in Modulating Dendritic Cell Responses toLeishmania amazonensisInfection

NK Cells Promote Type 1 T Cell Immunity through Modulating the Function of Dendritic Cells during Intracellular Bacterial Infection

NKG2D Receptor Signaling Enhances Cytolytic Activity by Virus-Specific CD8⁺T Cells: Evidence for a Protective Role in Virus-Induced Encephalitis

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NK Cells Enhance Dendritic Cell Response against Parasite Antigens via NKG2D Pathway

Cited by 68 publications

References 43 publications

Role of Natural Killer Cells in Modulating Dendritic Cell Responses toLeishmania amazonensisInfection

Role of Natural Killer Cells in Modulating Dendritic Cell Responses toLeishmania amazonensisInfection

NK Cells Promote Type 1 T Cell Immunity through Modulating the Function of Dendritic Cells during Intracellular Bacterial Infection

NKG2D Receptor Signaling Enhances Cytolytic Activity by Virus-Specific CD8+T Cells: Evidence for a Protective Role in Virus-Induced Encephalitis

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NKG2D Receptor Signaling Enhances Cytolytic Activity by Virus-Specific CD8⁺T Cells: Evidence for a Protective Role in Virus-Induced Encephalitis