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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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Mo-DCs produce significantly less iNOS during infection with L. mexicana compared to L. major.C57BL/6 mice were infected and ears were processed as above. In addition to staining for surface markers, intracellular staining for iNOS was performed. Percentage (A) or absolute number (B) of iNOS-producing cells in the ear of naïve or infected mice on day 14. Cells are previously gated on live, singlets that are CD11bhi CD11c+. The results expressed are the mean percentage (± SD for FACS plots) or the mean number of cells (± SE for the bar graph) of 3 mice per group. The results are representative of two experiments. * significantly lower (p<0.05) compared to L. major infected mice.
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pntd-0001858-g003: Mo-DCs produce significantly less iNOS during infection with L. mexicana compared to L. major.C57BL/6 mice were infected and ears were processed as above. In addition to staining for surface markers, intracellular staining for iNOS was performed. Percentage (A) or absolute number (B) of iNOS-producing cells in the ear of naïve or infected mice on day 14. Cells are previously gated on live, singlets that are CD11bhi CD11c+. The results expressed are the mean percentage (± SD for FACS plots) or the mean number of cells (± SE for the bar graph) of 3 mice per group. The results are representative of two experiments. * significantly lower (p<0.05) compared to L. major infected mice.

Mentions: Although there were fewer monocytes recruited to lesions from L. mexicana infected mice compared with those from L. major infected mice, the ratio of monocytes to mo-DCs was similar (Fig. 2). In these experiments we did not determine if the CD11c+ Ly6C+ cells were derived from monocytes, but based on previous findings [24], this is our assumption. However, mo-DCs in the lesions from L. mexicana infected mice expressed significantly less iNOS compared with mo-DCs from L. major lesions. Thus, while approximately 20% of the mo-DCs in lesions from L. major infected mice were iNOS+, only 3% were iNOS+ in lesions from L. mexicana infected mice (Fig. 3A). Similarly, the number of iNOS-producing mo-DCs was significantly reduced in lesions from mice infected with L. mexicana (Fig. 3B). CD11bhi CD11c− Ly6C+, inflammatory monocytes, did not make iNOS in either L. major or L. mexicana infected mice (data not shown). These data demonstrate that there are fewer iNOS-producing mo-DCs in L. mexicana infected mice, potentially contributing to the inability of these mice to resolve their infection.


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)

Mo-DCs produce significantly less iNOS during infection with L. mexicana compared to L. major.C57BL/6 mice were infected and ears were processed as above. In addition to staining for surface markers, intracellular staining for iNOS was performed. Percentage (A) or absolute number (B) of iNOS-producing cells in the ear of naïve or infected mice on day 14. Cells are previously gated on live, singlets that are CD11bhi CD11c+. The results expressed are the mean percentage (± SD for FACS plots) or the mean number of cells (± SE for the bar graph) of 3 mice per group. The results are representative of two experiments. * significantly lower (p<0.05) compared to L. major infected mice.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3475671&req=5

pntd-0001858-g003: Mo-DCs produce significantly less iNOS during infection with L. mexicana compared to L. major.C57BL/6 mice were infected and ears were processed as above. In addition to staining for surface markers, intracellular staining for iNOS was performed. Percentage (A) or absolute number (B) of iNOS-producing cells in the ear of naïve or infected mice on day 14. Cells are previously gated on live, singlets that are CD11bhi CD11c+. The results expressed are the mean percentage (± SD for FACS plots) or the mean number of cells (± SE for the bar graph) of 3 mice per group. The results are representative of two experiments. * significantly lower (p<0.05) compared to L. major infected mice.
Mentions: Although there were fewer monocytes recruited to lesions from L. mexicana infected mice compared with those from L. major infected mice, the ratio of monocytes to mo-DCs was similar (Fig. 2). In these experiments we did not determine if the CD11c+ Ly6C+ cells were derived from monocytes, but based on previous findings [24], this is our assumption. However, mo-DCs in the lesions from L. mexicana infected mice expressed significantly less iNOS compared with mo-DCs from L. major lesions. Thus, while approximately 20% of the mo-DCs in lesions from L. major infected mice were iNOS+, only 3% were iNOS+ in lesions from L. mexicana infected mice (Fig. 3A). Similarly, the number of iNOS-producing mo-DCs was significantly reduced in lesions from mice infected with L. mexicana (Fig. 3B). CD11bhi CD11c− Ly6C+, inflammatory monocytes, did not make iNOS in either L. major or L. mexicana infected mice (data not shown). These data demonstrate that there are fewer iNOS-producing mo-DCs in L. mexicana infected mice, potentially contributing to the inability of these mice to resolve their infection.

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