Cytokines in the differentiation of Th1/Th2 CD4+ subsets in leishmaniasis

Reiner, Steven L.; Locksley, Richard M.

doi:10.1002/jcb.240530409

Cited by 34 publications

(17 citation statements)

References 37 publications

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“…The Gr-1 + cells may represent neutrophils that largely respond to CXC chemokines. C57Bl/6 mice produce a Th1 dominant inflammatory response to LPS (Reiner & Locksley, 1993;Takeda et al, 2003) typical of a viral infection. Nevertheless, the dynamics of the cutaneous response induced with LPS will differ from that resulting from viral infection.…”

Section: Cd11bmentioning

confidence: 99%

Orf virus-encoded chemokine-binding protein is a potent inhibitor of inflammatory monocyte recruitment in a mouse skin model

Lateef

Baird

Wise

et al. 2009

Journal of General Virology

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The parapoxvirus orf virus causes pustular dermatitis in sheep and is transmissible to humans. The virus encodes a secreted chemokine-binding protein (CBP). We examined the ability of this protein to inhibit migration of murine monocytes in response to CC inflammatory chemokines, using chemotaxis assays, and its effects on monocyte recruitment into the skin, using a mouse model in which inflammation was induced with bacterial lipopolysaccharide. CBP was shown to bind murine chemokines CCL2, CCL3 and CCL5 with high affinity by surface plasmon resonance and it completely inhibited chemokine-induced migration of monocytes at a CBP : chemokine molar ratio of 4 : 1. In the mouse, low levels of CBP potently inhibited the recruitment of Gr-1 + / CD11b + monocytes to the site of inflammation in the skin but had little effect on neutrophil recruitment, suggesting that this factor plays a role in disrupting chemokine-induced recruitment of specific immune cell types to infection sites.

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Section: Cd11bmentioning

confidence: 99%

Orf virus-encoded chemokine-binding protein is a potent inhibitor of inflammatory monocyte recruitment in a mouse skin model

Lateef

Baird

Wise

et al. 2009

Journal of General Virology

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“…The polarization of the immune response is enhanced when chronic exposure to an agent occurs, such as with persistent infections or exposure to environmental toxins. Further, polarization of the immune response to Th1 or Th2 cytokines is under genetic control, as demonstrated by divergent responses of different inbred strains of mice to experimental murine leishmaniasis (10,11). Genetically resistant mice, such as C57BL͞6 mice exhibit an expansion of IFN-␥-producing Th1 cells and control the infection, whereas susceptible strains such as BALB͞c mice develop an IL-4 mediated Th2 response (10,12,13).…”

mentioning

confidence: 99%

“…In the context of these data, as well as that indicating that IFN-␥ is a key component of the Th1 cytokine pathway (10,12), we hypothesized that the immune response and specifically Th1 and Th2 cytokines could be involved in the fibrogenic response to hepatic injury. To examine the role of Th1 and Th2 cytokines in hepatic fibrosis, we analyzed the fibrogenic responses of BALB͞c and C57BL͞6 mice in toxin-induced hepatic injury.…”

mentioning

confidence: 99%

Strain-specific differences in mouse hepatic wound healing are mediated by divergent T helper cytokine responses

Shi

Wakil

Rockey

1997

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

294

193

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Hepatic fibrosis represents the generalized response of the liver to injury and is characterized by excessive deposition of extracellular matrix. The cellular basis of this process is complex and involves interplay of many factors, of which cytokines are prominent. We have identified divergent fibrosing responses to injury among mouse strains and taken advantage of these differences to examine and contrast T helper (Th)-derived cytokines during fibrogenesis. Liver injury was induced with carbon tetrachloride, fibrosis was quantitated, and Th1͞Th2 cytokine mRNAs measured. Liver injury in BALB͞c mice resulted in severe fibrosis, whereas C57BL͞6 mice developed comparatively minimal fibrosis. Fibrogenesis was significantly modified in T and B celldeficient BALB͞c and C57BL͞6 severe combined immunodeficient (SCID) mice compared with wild-type counterparts, suggesting a role of Th subsets. Fibrogenic BALB͞c mice exhibited a Th2 response during the wounding response, whereas C57BL͞6 mice displayed a Th1 response, suggesting that hepatic fibrosis is inf luenced by different T helper subsets. Moreover, mice lacking interferon ␥, which default to the Th2 cytokine pathway, exhibited more pronounced fibrotic lesions than did wild-type animals. Finally, shifting of the Th2 response toward a Th1 response by treatment with neutralizing anti-interleukin 4 or with interferon ␥ itself ameliorated fibrosis in BALB͞c mice. These data support a role for immune modulation of hepatic fibrosis and suggest that Th cytokine subsets can modulate the fibrotic response to injury.

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“…Resistance to L. major is mediated by IFN-␥-producing CD4 ϩ Th1 cells whose induction is dependent on IL-12 produced by dendritic cells (DCs) (24,(33)(34)(35). Given that deficiency of mLT results in the resistant mice becoming sensitive to L. major, we determined whether this was due to impaired IL-12 induction and defective Th1 cell response.…”

Section: Late Impaired Production Of Il-12 Ifn-␥ and Nomentioning

confidence: 99%

Lymphotoxin αβ2 (Membrane Lymphotoxin) Is Critically Important for Resistance to Leishmania major Infection in Mice

Liu²,

Fan

et al. 2007

The Journal of Immunology

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Although the essential role of TNF-α in the control of intracellular pathogens including Leishmania major is well established, it is uncertain whether the related cytokine lymphotoxin αβ2 (LTα1β2, membrane lymphotoxin) plays any role in this process. In this study, we investigated the contribution of membrane lymphotoxin in host response to L. major infection by using LTβ-deficient (LTβ−/−) mice on the resistant C57BL/6 background. Despite mounting early immune responses comparable to those of wild-type (WT) mice, LTβ−/− mice developed chronic nonhealing cutaneous lesions due to progressive and unresolving inflammation that is accompanied by uncontrolled parasite proliferation. This chronic disease was associated with striking reduction in IL-12 and Ag-specific IFN-γ production by splenocytes from infected mice. Consistent with defective cellular immune response, infected LTβ−/− mice had significantly low Ag-specific serum IgG1 and IgG2a levels compared with WT mice. Although administration of rIL-12 to L. major-infected LTβ−/− mice caused complete resolution of chronic lesions, it only partially (but significantly) reduced parasite proliferation. In contrast, blockade of LIGHT signaling in infected LTβ−/− mice resulted in acute and progressive lesion development, massive parasite proliferation, and dissemination to the visceral organs. Although infected LTβ−/− WT bone marrow chimeric mice were more resistant than LTβ−/− mice, they still had reduced ability to control parasites and showed defective IL-12 and IFN-γ production compared with infected WT mice. These results suggest that membrane lymphotoxin plays critical role in resistance to L. major by promoting effective T cell-mediated anti-Leishmania immunity.

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Cytokines in the differentiation of Th1/Th2 CD4+ subsets in leishmaniasis

Cited by 34 publications

References 37 publications

Orf virus-encoded chemokine-binding protein is a potent inhibitor of inflammatory monocyte recruitment in a mouse skin model

Orf virus-encoded chemokine-binding protein is a potent inhibitor of inflammatory monocyte recruitment in a mouse skin model

Strain-specific differences in mouse hepatic wound healing are mediated by divergent T helper cytokine responses

Lymphotoxin αβ2 (Membrane Lymphotoxin) Is Critically Important for Resistance to Leishmania major Infection in Mice

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