Understanding the role of monocytic cells in liver inflammation using parasite infection as a model

Bosschaerts, Tom; Guilliams, Martin; Stijlemans, Benoı̂t; Baetseĺier, Patrick De; Beck, Alain

doi:10.1016/j.imbio.2009.06.010

Cited by 24 publications

(35 citation statements)

References 83 publications

(119 reference statements)

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“…Given the important role that moDCs play in the innate immune responses against certain infections (8,47,48), it is possible that they are more functionally suited to degrading and removing potentially pathogenic Ag rather than retaining internalized peptides for presentation to T cells. This property is reminiscent of several populations of macrophages, which are professional phagocytes and share monocytic origins with moDCs (49).…”

Section: Discussionmentioning

confidence: 99%

Monocyte-Derived Dendritic Cells Promote Th Polarization, whereas Conventional Dendritic Cells Promote Th Proliferation

Chow

Lew

Sutherland

et al. 2016

The Journal of Immunology

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Monocyte-derived dendritic cells (moDCs) dramatically increase in numbers upon infection and inflammation; accordingly, we found that this also occurs during allogeneic responses. Despite their prominence, how emergent moDCs and resident conventional DCs (cDCs) divide their labor as APCs remain undefined. Hence, we compared both direct and indirect presentation by murine moDCs versus cDCs. We found that, despite having equivalent MHC class II expression and in vitro survival, moDCs were 20-fold less efficient than cDCs at inducing CD4+ T cell proliferation through both direct and indirect Ag presentation. Despite this, moDCs were more potent at inducing Th1 and Th17 differentiation (e.g., 8-fold higher IFN-γ and 2-fold higher IL-17A in T cell cocultures), whereas cDCs induced 10-fold higher IL-2 production. Intriguingly, moDCs potently reduced the ability of cDCs to stimulate T cell proliferation in vitro and in vivo, partially through NO production. We surmise that such division of labor between moDCs and cDCs has implications for their respective roles in the immune response.

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Section: Discussionmentioning

confidence: 99%

Monocyte-Derived Dendritic Cells Promote Th Polarization, whereas Conventional Dendritic Cells Promote Th Proliferation

Chow

Lew

Sutherland

et al. 2016

The Journal of Immunology

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“…The two parasite models share common features, including the critical role of CD11b + myeloid cells to control parasite growth or to induce tissue pathogenicity. More than 80% of the parasites are eliminated by liver myeloid cells and infected mice die from a systemic inflammatory response syndrome (SIRS) that is initiated by phagocytosis of parasites by liver myeloid cells and culminates in apoptosis/ necrosis of liver immune and parenchymal cells [31][32][33]. This review restricts on summarising the knowledge on the contribution of myeloid cells to hepatic injury.…”

Section: Reviewmentioning

confidence: 99%

“…Persistence of IFN-g-dependent M1-type myeloid cell activation initiated by phagocytosis of trypanosomes leads to liver lesions and SIRS, decreasing the tolerance and survival of infected mice [33,48] (Figure 2). Numerous immune mediators keep in check the tissue-destructive (type I IFN, TNF, and/or NO) versus the tissue-protective (IL-10) immune response [33,48,52].…”

Section: M2-type Myeloid Cells Contribute To Tolerance In the Mammalimentioning

confidence: 99%

African trypanosome control in the insect vector and mammalian host

Beck

Abbeele

Baetseĺier

et al. 2014

Trends in Parasitology

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“…T rypanosoma brucei species are protozoan parasites that cause severe disease and death to humans and animals in Africa (1)(2)(3)(4). The parasites have developed highly sophisticated mechanisms to escape host immune responses, including antigenic variation of the variant surface glycoprotein (VSG) (3,5), immunosuppression (4,6,7), and splenic B cell depletion (8,9).…”

mentioning

confidence: 99%

“…As a regulatory cytokine, IL-10 is required to downregulate macrophage activation (15,23,28). Thus, IFN-␥ and IL-10 play crucial roles in protective as well as pathological immune responses during African trypanosomiasis (1,4). CD4 ϩ and CD8 ϩ T cells are the major potential producers of IFN-␥ and IL-10.…”

mentioning

confidence: 99%

Distinct Contributions of CD4⁺and CD8⁺T Cells to Pathogenesis of Trypanosoma brucei Infection in the Context of Gamma Interferon and Interleukin-10

Liu

Sun

et al. 2015

Infect Immun

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T rypanosoma brucei species are protozoan parasites that cause severe disease and death to humans and animals in Africa (1-4). The parasites have developed highly sophisticated mechanisms to escape host immune responses, including antigenic variation of the variant surface glycoprotein (VSG) (3, 5), immunosuppression (4, 6, 7), and splenic B cell depletion (8, 9). For practical and ethical reasons, mouse models have become an alternative and have proven to be a cornerstone for studying African trypanosomiasis of humans and domestic animals (2). BALB/c mice are highly susceptible to T. brucei and Trypanosoma congolense infections, whereas C57BL/6 mice are relatively resistant, as measured by levels of parasitemia, immunosuppression, and survival time (10-12). Immunological experiments are often performed using C57BL/6 mice, because most of the gene-deficient mice available have the C57BL/6 background.Early studies showed that clearance of the parasites takes place mainly in the liver (13,14). Further studies demonstrated that the parasites are cleared by Kupffer cells via phagocytosis (15), which is mediated by IgM as well as IgG antibodies (Abs) specific for VSG (16,17). More recently, using IgM-deficient and B cell-deficient mice, it has been shown that IgG, but not IgM, Abs play a dominant role in the clearance of the parasites (18,19). Gamma interferon (IFN-␥), produced by VSG-specific T cell receptor ␣␤-positive (TCR␣␤ ϩ ) CD4 ϩ T cells (20), is critical for host resistance to African trypanosomes (18,(21)(22)(23)(24). It is likely that IFN-␥ exerts its protective effect through macrophage activation, resulting in secretion of tumor necrosis factor alpha (TNF-␣) and nitric oxide, which mediate parasite lysis or death (18,(25)(26)(27). However, overactivation of macrophages driven by excessive production of IFN-␥, particularly in the absence of interleukin-10 (IL-10) signaling, induces liver pathology, which kills the infected mice (15,28,29). As a regulatory cytokine, IL-10 is required to downregulate macrophage activation (15,23,28). Thus, IFN-␥ and IL-10 play crucial roles in protective as well as pathological immune responses during African trypanosomiasis (1, 4). CD4 ϩ and CD8 ϩ T cells are the major potential producers of IFN-␥ and IL-10. Although the important roles of IFN-␥ and IL-10 in the pathogenesis of African trypanosomiasis have been documented, the roles of CD4 ϩ and CD8 ϩ T cells in the development of the disease are not fully understood. In this study, we evaluated the contributions of CD4 ϩ and CD8 ϩ T cells to the pathogenesis of this disease. In particular, we focused on how their contributions were related to IFN-␥ and IL-10. MATERIALS AND METHODSMice. Female 8-to 10-week-old BALB/c AnNCrlBR (BALB/c) mice and 5-to 6-week-old female outbred Swiss white mice (CD1) were purchased from the National Cancer Institute (Frederick, MD). CD4Ϫ/Ϫ and

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Understanding the role of monocytic cells in liver inflammation using parasite infection as a model

Cited by 24 publications

References 83 publications

Monocyte-Derived Dendritic Cells Promote Th Polarization, whereas Conventional Dendritic Cells Promote Th Proliferation

Monocyte-Derived Dendritic Cells Promote Th Polarization, whereas Conventional Dendritic Cells Promote Th Proliferation

African trypanosome control in the insect vector and mammalian host

Distinct Contributions of CD4⁺and CD8⁺T Cells to Pathogenesis of Trypanosoma brucei Infection in the Context of Gamma Interferon and Interleukin-10

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Understanding the role of monocytic cells in liver inflammation using parasite infection as a model

Cited by 24 publications

References 83 publications

Monocyte-Derived Dendritic Cells Promote Th Polarization, whereas Conventional Dendritic Cells Promote Th Proliferation

Monocyte-Derived Dendritic Cells Promote Th Polarization, whereas Conventional Dendritic Cells Promote Th Proliferation

African trypanosome control in the insect vector and mammalian host

Distinct Contributions of CD4+and CD8+T Cells to Pathogenesis of Trypanosoma brucei Infection in the Context of Gamma Interferon and Interleukin-10

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Distinct Contributions of CD4⁺and CD8⁺T Cells to Pathogenesis of Trypanosoma brucei Infection in the Context of Gamma Interferon and Interleukin-10