CCR7 facilitates the pro-inflammatory function of dendritic cells in experimental leishmaniasis
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Updated: May 4, 2026
In vivo Imaging of Transgenic Leishmania Parasites in a Live Host
Published on: July 27, 2010
1Menzies Research Institute Tasmania, Hobart, Tas, Australia; James Cook University, Townsville, Qld, Australia.
Abstract:
Cutaneous leishmaniasis, caused by the parasite Leishmania major, results in lesions at the site of infection, which are self-healing in resistant hosts. However, in the absence of the chemokine receptor CCR7, mice are unable to heal the lesion and develop chronic disease. These B6.CCR7(-/-) mice display an increased number of Th2 cells and immunosuppressive cytokine levels, as well as more regulatory T cells. As CCR7 is expressed on activated dendritic cells (DCs), and these cells require CCR7 to migrate to the draining lymph node, we expected decreased migration of DCs into the lymph node in the absence of CCR7 during cutaneous leishmaniasis. Consequently, in an attempt to initiate a self-healing response, we adoptively transferred CCR7(+) (B6.WT) DCs into the site of infection of B6.CCR7(-/-) mice. Surprisingly, instead of healing the lesion, B6.CCR7(-/-) mice inoculated with B6.WT DCs developed augmented lesions and showed increased immunosuppression compared to control B6.CCR7(-/-) mice transferred with B6.CCR7(-/-) DCs or B6.WT mice with B6.WT DCs. Finally, B6.WT mice injected with B6.CCR7(-/-) DCs also presented delayed healing of the lesion. These results indicate that CCR7 must be expressed on DCs, as well as peripheral cells, to allow an efficient immune response to L. major.
Insights
Chemokine receptor CCR7 is crucial for healing cutaneous leishmaniasis. Its absence in dendritic cells impairs immune response, worsening lesions and immunosuppression in mice.
Area of Science:
- Immunology
- Parasitology
- Dermatology
Background:
- Cutaneous leishmaniasis, caused by Leishmania major, typically self-heals in resistant hosts.
- Absence of chemokine receptor CCR7 leads to chronic disease in mice, characterized by Th2 cell expansion and increased immunosuppression.
- CCR7 is essential for dendritic cell (DC) migration to lymph nodes.
Purpose of the Study:
- To investigate the role of CCR7 in the immune response to Leishmania major infection.
- To determine if adoptive transfer of CCR7-expressing DCs can restore self-healing in CCR7-deficient mice.
Main Methods:
- Utilized B6.CCR7(-/-) mice, which lack CCR7, and B6.WT mice (wild-type).
- Adoptive transfer of CCR7(+) (B6.WT) dendritic cells (DCs) into the infection site of B6.CCR7(-/-) mice.
- Adoptive transfer of CCR7(-) (B6.CCR7(-/-)) DCs into B6.WT mice.
- Evaluated lesion development, immune cell populations (Th2, regulatory T cells), and cytokine profiles.
Main Results:
- B6.CCR7(-/-) mice receiving B6.WT DCs showed exacerbated lesions and increased immunosuppression compared to controls.
- B6.WT mice receiving B6.CCR7(-/-) DCs exhibited delayed lesion healing.
- CCR7 expression on DCs is critical for initiating an effective immune response against Leishmania major.
Conclusions:
- CCR7 on dendritic cells is essential for their migration and initiating a protective immune response.
- CCR7 expression on both DCs and peripheral cells is required for efficient resolution of Leishmania major infection.
- Disrupting CCR7 function in DCs exacerbates leishmaniasis, highlighting its critical role in host defense.
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