Limits...
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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Related in: MedlinePlus

Fewer FITC+ endogenous mo-DCs migrate to the dLN during L. mexicana infection compared to L. major.C57BL/6 mice were infected as above for two weeks. FITC isomer was applied to the ears of naïve, L. major or L. mexicana infected mice on day 14 and dLNs were harvested and processed forty-eight hours later. FITC+ MHCIIhi CD11c+ cells were enumerated in the dLNs. These cells are previously gated on live, singlets that are CD11bhi. The results expressed are the mean number of cells (± SE) of 3 mice per group. The results are representative of two experiments. * significantly different (p<0.05) between indicated groups.
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pntd-0001858-g004: Fewer FITC+ endogenous mo-DCs migrate to the dLN during L. mexicana infection compared to L. major.C57BL/6 mice were infected as above for two weeks. FITC isomer was applied to the ears of naïve, L. major or L. mexicana infected mice on day 14 and dLNs were harvested and processed forty-eight hours later. FITC+ MHCIIhi CD11c+ cells were enumerated in the dLNs. These cells are previously gated on live, singlets that are CD11bhi. The results expressed are the mean number of cells (± SE) of 3 mice per group. The results are representative of two experiments. * significantly different (p<0.05) between indicated groups.

Mentions: To evaluate the ability of DCs to migrate from the site of infection, C57BL/6 mice were infected in the ear with L. major or L. mexicana and two weeks post-infection the ears were FITC painted. After 48 hours we compared the FITC+ DCs (CD11c+ MHCIIhi) in the draining lymph node from naïve, L. major infected or L. mexicana infected mice. Notably, there were significantly more FITC+ DCs in L. major infected mice when compared to either naïve or L. mexicana infected mice. In contrast, there was no difference in the number of FITC+ DCs between naïve and L. mexicana infected mice (Fig. 4), indicating that mo-DCs migration to the dLN is compromised in L. mexicana infected mice.


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)

Fewer FITC+ endogenous mo-DCs migrate to the dLN during L. mexicana infection compared to L. major.C57BL/6 mice were infected as above for two weeks. FITC isomer was applied to the ears of naïve, L. major or L. mexicana infected mice on day 14 and dLNs were harvested and processed forty-eight hours later. FITC+ MHCIIhi CD11c+ cells were enumerated in the dLNs. These cells are previously gated on live, singlets that are CD11bhi. The results expressed are the mean number of cells (± SE) of 3 mice per group. The results are representative of two experiments. * significantly different (p<0.05) between indicated groups.
© Copyright Policy
Related In: Results  -  Collection

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

pntd-0001858-g004: Fewer FITC+ endogenous mo-DCs migrate to the dLN during L. mexicana infection compared to L. major.C57BL/6 mice were infected as above for two weeks. FITC isomer was applied to the ears of naïve, L. major or L. mexicana infected mice on day 14 and dLNs were harvested and processed forty-eight hours later. FITC+ MHCIIhi CD11c+ cells were enumerated in the dLNs. These cells are previously gated on live, singlets that are CD11bhi. The results expressed are the mean number of cells (± SE) of 3 mice per group. The results are representative of two experiments. * significantly different (p<0.05) between indicated groups.
Mentions: To evaluate the ability of DCs to migrate from the site of infection, C57BL/6 mice were infected in the ear with L. major or L. mexicana and two weeks post-infection the ears were FITC painted. After 48 hours we compared the FITC+ DCs (CD11c+ MHCIIhi) in the draining lymph node from naïve, L. major infected or L. mexicana infected mice. Notably, there were significantly more FITC+ DCs in L. major infected mice when compared to either naïve or L. mexicana infected mice. In contrast, there was no difference in the number of FITC+ DCs between naïve and L. mexicana infected mice (Fig. 4), indicating that mo-DCs migration to the dLN is compromised in L. mexicana infected mice.

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