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Leishmania mexicana induces limited recruitment and activation of monocytes and monocyte-derived dendritic cells early during infection.

Petritus PM, Manzoni-de-Almeida D, Gimblet C, Gonzalez Lombana C, Scott P - PLoS Negl Trop Dis (2012)

Bottom Line: Moreover, monocytes that differentiate into mo-DCs in L. mexicana lesions produced less iNOS and migrated less efficiently to the draining lymph node as compared to those from L. major infected mice.Treatment of L. mexicana infected mice with α-IL-10R antibody resulted in increased recruitment of monocytes to the lesion along with greater production of IFN-γ and iNOS.Taken together, these data suggest that during L. mexicana infection reduced recruitment, activation and subsequent migration of monocytes and mo-DCs to the draining lymph nodes may result in the insufficient priming of a Th1 response.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.

ABSTRACT
While C57BL/6 mice infected in the ear with L. major mount a vigorous Th1 response and resolve their lesions, the Th1 response in C57BL/6 mice infected with L. mexicana is more limited, resulting in chronic, non-healing lesions. The aim of this study was to determine if the limited immune response following infection with L. mexicana is related to a deficiency in the ability of monocyte-derived dendritic cells (mo-DCs) to prime a sufficient Th1 response. To address this issue we compared the early immune response following L. mexicana infection with that seen in L. major infected mice. Our data show that fewer monocytes are recruited to the lesions of L. mexicana infected mice as compared to mice infected with L. major. Moreover, monocytes that differentiate into mo-DCs in L. mexicana lesions produced less iNOS and migrated less efficiently to the draining lymph node as compared to those from L. major infected mice. Treatment of L. mexicana infected mice with α-IL-10R antibody resulted in increased recruitment of monocytes to the lesion along with greater production of IFN-γ and iNOS. Additionally, injection of DCs into the ear at the time of infection with L. mexicana also led to a more robust Th1 response. Taken together, these data suggest that during L. mexicana infection reduced recruitment, activation and subsequent migration of monocytes and mo-DCs to the draining lymph nodes may result in the insufficient priming of a Th1 response.

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DCs injected at the time of infection with L. mexicana lead to a more robust Th1 response.C57BL/6 mice were infected as before in the ear with L. mexicana, however, one group also received DCs that were derived in vitro. At two weeks post-infection ears and dLNs were processed. (A) Levels of IFN-γ (ng/mL) from the supernatants of single cell suspensions from the dLN of each group that were stimulated for 72 hours with L. mexicana freeze-thaw antigen. (B) Percentage and absolute number of iNOS-producing cells in the ear of L. mexicana infected mice or L. mexicana infected mice that received DCs. Cells are previously gated on live, singlets that are CD11bhi CD11c+. (C) The cellularity of the dLN in L. mexicana infected mice or L. mexicana infected mice that received DCs. The results expressed are the mean percentage (± SD for FACS plots) or the mean number of cells (± SE for bar graphs) of 2–4 mice per group. The results are representative of two experiments. * significantly higher (p<0.05) compared to L. mexicana infected mice.
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pntd-0001858-g007: DCs injected at the time of infection with L. mexicana lead to a more robust Th1 response.C57BL/6 mice were infected as before in the ear with L. mexicana, however, one group also received DCs that were derived in vitro. At two weeks post-infection ears and dLNs were processed. (A) Levels of IFN-γ (ng/mL) from the supernatants of single cell suspensions from the dLN of each group that were stimulated for 72 hours with L. mexicana freeze-thaw antigen. (B) Percentage and absolute number of iNOS-producing cells in the ear of L. mexicana infected mice or L. mexicana infected mice that received DCs. Cells are previously gated on live, singlets that are CD11bhi CD11c+. (C) The cellularity of the dLN in L. mexicana infected mice or L. mexicana infected mice that received DCs. The results expressed are the mean percentage (± SD for FACS plots) or the mean number of cells (± SE for bar graphs) of 2–4 mice per group. The results are representative of two experiments. * significantly higher (p<0.05) compared to L. mexicana infected mice.

Mentions: The previous experiment, where L. mexicana infected mice were treated with α-IL-10R antibody, suggests that the increase in mo-DCs in the lesion may result in the priming of an improved Th1 response. Here, we test whether there is a correlation between increased numbers of DCs in the lesion and a more robust Th1 response. We injected DCs into the ear at the time of infection with L. mexicana and we compared the Th1 response 14 days post-infection to L. mexicana infected mice receiving no DCs. As predicted, L. mexicana infected mice receiving DCs produced greater levels of IFN-γ (Fig. 7A), and had a greater percentage and number of iNOS-producing DCs (Fig. 7B). Moreover, the impaired lymph node expansion that occurs during infection with L. mexicana was overcome in mice that received DCs (Fig. 7C). Taken together, these data suggest that the limited Th1 response observed in L. mexicana infected mice can be overcome if a greater number of DCs can be established in the lesion.


Leishmania mexicana induces limited recruitment and activation of monocytes and monocyte-derived dendritic cells early during infection.

Petritus PM, Manzoni-de-Almeida D, Gimblet C, Gonzalez Lombana C, Scott P - PLoS Negl Trop Dis (2012)

DCs injected at the time of infection with L. mexicana lead to a more robust Th1 response.C57BL/6 mice were infected as before in the ear with L. mexicana, however, one group also received DCs that were derived in vitro. At two weeks post-infection ears and dLNs were processed. (A) Levels of IFN-γ (ng/mL) from the supernatants of single cell suspensions from the dLN of each group that were stimulated for 72 hours with L. mexicana freeze-thaw antigen. (B) Percentage and absolute number of iNOS-producing cells in the ear of L. mexicana infected mice or L. mexicana infected mice that received DCs. Cells are previously gated on live, singlets that are CD11bhi CD11c+. (C) The cellularity of the dLN in L. mexicana infected mice or L. mexicana infected mice that received DCs. The results expressed are the mean percentage (± SD for FACS plots) or the mean number of cells (± SE for bar graphs) of 2–4 mice per group. The results are representative of two experiments. * significantly higher (p<0.05) compared to L. mexicana infected mice.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3475671&req=5

pntd-0001858-g007: DCs injected at the time of infection with L. mexicana lead to a more robust Th1 response.C57BL/6 mice were infected as before in the ear with L. mexicana, however, one group also received DCs that were derived in vitro. At two weeks post-infection ears and dLNs were processed. (A) Levels of IFN-γ (ng/mL) from the supernatants of single cell suspensions from the dLN of each group that were stimulated for 72 hours with L. mexicana freeze-thaw antigen. (B) Percentage and absolute number of iNOS-producing cells in the ear of L. mexicana infected mice or L. mexicana infected mice that received DCs. Cells are previously gated on live, singlets that are CD11bhi CD11c+. (C) The cellularity of the dLN in L. mexicana infected mice or L. mexicana infected mice that received DCs. The results expressed are the mean percentage (± SD for FACS plots) or the mean number of cells (± SE for bar graphs) of 2–4 mice per group. The results are representative of two experiments. * significantly higher (p<0.05) compared to L. mexicana infected mice.
Mentions: The previous experiment, where L. mexicana infected mice were treated with α-IL-10R antibody, suggests that the increase in mo-DCs in the lesion may result in the priming of an improved Th1 response. Here, we test whether there is a correlation between increased numbers of DCs in the lesion and a more robust Th1 response. We injected DCs into the ear at the time of infection with L. mexicana and we compared the Th1 response 14 days post-infection to L. mexicana infected mice receiving no DCs. As predicted, L. mexicana infected mice receiving DCs produced greater levels of IFN-γ (Fig. 7A), and had a greater percentage and number of iNOS-producing DCs (Fig. 7B). Moreover, the impaired lymph node expansion that occurs during infection with L. mexicana was overcome in mice that received DCs (Fig. 7C). Taken together, these data suggest that the limited Th1 response observed in L. mexicana infected mice can be overcome if a greater number of DCs can be established in the lesion.

Bottom Line: Moreover, monocytes that differentiate into mo-DCs in L. mexicana lesions produced less iNOS and migrated less efficiently to the draining lymph node as compared to those from L. major infected mice.Treatment of L. mexicana infected mice with α-IL-10R antibody resulted in increased recruitment of monocytes to the lesion along with greater production of IFN-γ and iNOS.Taken together, these data suggest that during L. mexicana infection reduced recruitment, activation and subsequent migration of monocytes and mo-DCs to the draining lymph nodes may result in the insufficient priming of a Th1 response.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.

ABSTRACT
While C57BL/6 mice infected in the ear with L. major mount a vigorous Th1 response and resolve their lesions, the Th1 response in C57BL/6 mice infected with L. mexicana is more limited, resulting in chronic, non-healing lesions. The aim of this study was to determine if the limited immune response following infection with L. mexicana is related to a deficiency in the ability of monocyte-derived dendritic cells (mo-DCs) to prime a sufficient Th1 response. To address this issue we compared the early immune response following L. mexicana infection with that seen in L. major infected mice. Our data show that fewer monocytes are recruited to the lesions of L. mexicana infected mice as compared to mice infected with L. major. Moreover, monocytes that differentiate into mo-DCs in L. mexicana lesions produced less iNOS and migrated less efficiently to the draining lymph node as compared to those from L. major infected mice. Treatment of L. mexicana infected mice with α-IL-10R antibody resulted in increased recruitment of monocytes to the lesion along with greater production of IFN-γ and iNOS. Additionally, injection of DCs into the ear at the time of infection with L. mexicana also led to a more robust Th1 response. Taken together, these data suggest that during L. mexicana infection reduced recruitment, activation and subsequent migration of monocytes and mo-DCs to the draining lymph nodes may result in the insufficient priming of a Th1 response.

Show MeSH
Related in: MedlinePlus