Leishmania major H-line attenuated under pressure of gentamicin, induces a Th1 response which protects susceptible BALB/c mice against infection with virulent L. major

Parasitology ◽  
2009 ◽  
Vol 136 (11) ◽  
pp. 1243-1250 ◽  
Author(s):  
HAMID DANESHVAR ◽  
RICHARD BURCHMORE ◽  
PAUL HAGAN ◽  
R. STEPHEN PHILLIPS
Keyword(s):  
Immune Response ◽  
Lymph Node ◽  
Cell Line ◽  
Leishmania Major ◽  
Wild Type ◽  
Th1 Response ◽  
Th2 Responses ◽  
Draining Lymph Node ◽  
Ifn Γ

SUMMARYAn attenuated line of Leishmania major (L. major H-line) has been established by culturing promastigotes in vitro under gentamicin pressure. A modification of the previously described method for the generation of attenuated L. major is described, giving rise to attenuated parasites after 8 rather than 12 subpassages. No lesions developed in BALB/c mice infected with L. major H-line, whereas L. major wild-type (WT) induced a Th2 like response with progressive lesions. Analysis of splenocyte IFN-γ and IL-4 production following stimulation with promastigotes shows that the L. major H-line preferentially induces Th1-like responses and possibly down-regulates Th2 responses in BALB/c mice. L. major H-line parasites remained localized in the skin and draining lymph node, whereas L. major WT parasites disseminated into the visceral organs of BALB/c mice. Mice infected with L. major H-line acquired some resistance against L. major WT. These results show that the attenuated cell line of L. major is not only avirulent but that it may also modulate the host immune response.

scholarly journals Obesity impairs resistance to Leishmania major infection in C57BL/6 mice

2018 ◽  
Author(s):  
Franciele Carolina Silva ◽  
Vinicius Dantas Martins ◽  
Felipe Caixeta ◽  
Matheus Batista Carneiro ◽  
Graziele Ribeiro Goes ◽  
...  
Keyword(s):  
Immune Response ◽  
Lymph Node ◽  
Leishmania Major ◽  
Parasite Burden ◽  
Public Health Problem ◽  
Obese Mice ◽  
Obese People ◽  
Diet Induced Obesity ◽  
Draining Lymph Node

AbstractAn association between increased susceptibility to infectious diseases and obesity has been described as a result of impaired immunity in obese individuals. It is not clear whether a similar linkage can be drawn between obesity and parasitic diseases. To evaluate the effect of obesity in the immune response to cutaneous L. major infection, we studied the ability of C57BL/6 mice submitted to a high fat and sugar diet to control leishmaniasis. Mice with diet-induced obesity presented thicker lesions with higher parasite burden and more inflammatory infiltrate in the infected ear when infected with L. major. We observe no difference in IFN-γ or IL-4 production by draining lymph node cells between control and obese mice, but obese mice presented higher production of IgG1 and IL-17. A higher percentage of in vitro-infected peritoneal macrophages was found when these cells were obtained from obese mice when compared to lean mice. In vitro stimulation of macrophages with IL-17 decreased the capacity of cells from control mice to kill the parasite. Moreover, macrophages from obese mice presented higher arginase activity. Together our results indicate that diet-induced obesity impairs resistance to L. major in C57BL/6 mice without affecting the development of Th1 response.Author SummaryThe obesity is a public health problem and it is reaching extraordinary numbers in the world and others diseases are being involved and aggravated as consequence of obesity. What we know is that some diseases are more severe in obese people than in normal people. We did not know how obesity changes the profile of immune response to infectious agents, leading to the more severe diseases. That‘s why we decided to investigate how obese mice lead with Leishmania major infection. Leishmaniasis is a protozoa parasite infection considered a neglected disease. To try our hypothesis we gave a hipercaloric diet to induce obesity in C57BL/6 mice. After that, we injected L. major in the mice ear and followed the lesion for 8 weeks. We observed a ticker lesion and the cells from draining lymph node from obese mice produced more IL-17 than cells from normal mice. We also infected in vitro, macrophages from obese mice and stimulated the cells with IL-17, and we observed that the macrophages from obese mice are more infected by the L. major and it is worst in the presence of IL-17. Our results suggest that diet induced obesity decrease the resistance to infection.

scholarly journals Heterogeneity of Wild Leishmania major Isolates in Experimental Murine Pathogenicity and Specific Immune Response

2001 ◽  
Vol 69 (8) ◽  
pp. 4906-4915 ◽  
Author(s):  
C. Kébaı̈er ◽  
H. Louzir ◽  
M. Chenik ◽  
A. Ben Salah ◽  
K. Dellagi
Keyword(s):  
Immune Response ◽  
Lymph Node ◽  
Leishmania Major ◽  
Mononuclear Cells ◽  
Severe Disease ◽  
Interleukin 4 ◽  
Zoonotic Cutaneous Leishmaniasis ◽  
Tunisian Patients ◽  
Ifn Γ

ABSTRACT Virulence variability was investigated by analyzing the experimental pathogenicity of 19 Leishmania major strains in susceptible BALB/c mice. Twelve strains were isolated from Tunisian patients with zoonotic cutaneous leishmaniasis; seven strains were isolated in Syria (n = 1), Saudi Arabia (n = 2), Jordan (n = 2), or Israel (n = 2). BALB/c mice were injected in the hind footpad with 2 × 106 amastigotes of the various isolates, and lesion progression was recorded weekly for 9 weeks. Interleukin-4 (IL-4) and gamma interferon (IFN-γ) production of lymph node mononuclear cells activated in vitro with parasite antigens were evaluated 5 weeks after infection. We show that disease progression induced by different L. major isolates was largely heterogeneous although reproducible results were obtained when using the same isolate. Interestingly, isolates from the Middle East induced a more severe disease than did the majority of Tunisian isolates. Strains with the highest virulence tend to generate more IL-4 and less IFN-γ in vitro at week 5 postinfection as well as higher levels of early IL-4 mRNA in the lymph node draining the inoculation site at 16 h postinfection. These results suggest that L. major isolates from the field may differ in virulence, which influences the course of the disease induced in mice and the type of immune response elicited by the infected host.

scholarly journals Migration-Inhibitory Factor Gene-Deficient Mice Are Susceptible to Cutaneous Leishmania major Infection

2001 ◽  
Vol 69 (2) ◽  
pp. 906-911 ◽  
Author(s):  
Abhay R. Satoskar ◽  
Marcelo Bozza ◽  
Miriam Rodriguez Sosa ◽  
Guoshing Lin ◽  
John R. David
Keyword(s):  
Migration Inhibitory Factor ◽  
Protective Immunity ◽  
Leishmania Major ◽  
Inhibitory Factor ◽  
Interleukin 4 ◽  
Wild Type ◽  
Leishmanicidal Activity ◽  
Ifn Γ ◽  
Deficient Mice

ABSTRACT To determine the role of endogenous migration-inhibitory factor (MIF) in the development of protective immunity against cutaneous leishmaniasis, we analyzed the course of cutaneous Leishmania major infection in MIF gene-deficient mice (MIF−/−) and wild-type (MIF+/+) mice. Following cutaneous L. major infection, MIF−/− mice were susceptible to disease and developed significantly larger lesions and greater parasite burdens than MIF+/+ mice. Interestingly, antigen-stimulated lymph node cells from MIF−/− mice produced more interleukin-4 (IL-4) and gamma interferon (IFN-γ) than those from MIF+/+ mice, although the differences were statistically not significant. IFN-γ-activated resting peritoneal macrophages from MIF−/− mice showed impaired macrophage leishmanicidal activity and produced significantly lower levels of nitric oxide and superoxide in vitro. The macrophages from MIF−/− mice, however, produced much more IL-6 than macrophages from wild-type mice. These findings demonstrate that endogenous MIF plays an important role in the development of protective immunity against L. majorin vivo. Furthermore, they indicate that the susceptibility of MIF−/− mice to L. major infection is due to impaired macrophage leishmanicidal activity rather than dysregulation of Th1 and Th2 responses.

scholarly journals Polarized Helper-T-Cell Responses againstLeishmania major in the Absence of B Cells

1999 ◽  
Vol 67 (1) ◽  
pp. 266-270 ◽  
Author(s):  
Daniel R. Brown ◽  
Steven L. Reiner
Keyword(s):  
T Cell ◽  
B Cells ◽  
Leishmania Major ◽  
Immunoglobulin M ◽  
Wild Type ◽  
Th2 Response ◽  
Th1 Response ◽  
Cell Responses ◽  
Th Cell ◽  
Th2 Responses

ABSTRACT B-cell-to-T-cell signaling can shape helper T (Th) cell responses. During infection with Leishmania major, Th response is critical in determining the outcome of disease. Resistance depends on the generation of a protective Th1 response, while susceptibility is mediated by the generation of a Th2 response. In this study, we determined whether B cells are required for the development of polarized Th1 and Th2 responses during infection with L. major. Mice lacking B cells due to disruption of the immunoglobulin M locus (μMT) were infected with L. major, and disease progression and Th cell development were assessed. On the genetically resistant C57BL background, both wild-type and μMT mice controlled the infection and mounted a Th1 response. On the genetically susceptible BALB/c background, both wild-type and μMT mice were susceptible to infection and generated Th2 responses. Thus, duringL. major infection, neither direct antigen presentation or costimulation by B cells nor antibody-mediated effector functions are essential for the development of polarized Th responses.

scholarly journals Allergen-induced dendritic cell migration is controlled through Substance P release by sensory neurons

2020 ◽  
Author(s):  
Pamela A. Aderhold ◽  
Zaynah N. A. Dewan ◽  
Caroline Perner ◽  
Cameron H. Flayer ◽  
Xueping Zhu ◽  
...  
Keyword(s):  
Immune Response ◽  
Lymph Node ◽  
Substance P ◽  
Sensory Neurons ◽  
Dendritic Cell Migration ◽  
Draining Lymph Node ◽  
Th2 Differentiation ◽  
Allergic Immune Response

SUMMARYDendritic cells (DCs) of the cDC2 lineage are necessary for the initiation of the allergic immune response and in the dermis are marked by their expression of CD301b. CD301b+ dermal DCs respond to allergens encountered in vivo, but not in vitro. This suggests that another cell in the dermis may sense allergens and relay that information to activate and induce the migration of CD301b+ DCs to the draining lymph node. Using a model of cutaneous allergen exposure, we show that allergens directly activate TRPV1+ sensory neurons leading to itch and pain behaviors. Allergen-activated sensory neurons release the neuropeptide Substance P, which stimulates proximally located CD301b+ DCs through MRGPRA1. Substance P induces CD301b+ DC migration to the draining lymph node where they initiate Th2 differentiation. Thus, sensory neurons act as primary sensors of allergens, linking exposure to activation of allergic-skewing DCs and the initiation of the allergic immune response.

scholarly journals Immune Responses in Cutaneous Leishmaniasis: in vitro Thelper1/Thelper2 Cy-tokine Profiles Using Live Versus Killed Leishmania major

2021 ◽  
Author(s):  
Akram Miramin-Mohammadi ◽  
Amir Javadi ◽  
Seyyed Ebrahim Eskandari ◽  
Mahmood Nateghi-Rostami ◽  
Ali Khamesipour
Keyword(s):  
Immune Response ◽  
Cutaneous Leishmaniasis ◽  
Leishmania Major ◽  
Mononuclear Cells ◽  
Control Measure ◽  
Peripheral Blood Mononuclear ◽  
Significant Difference ◽  
History Of ◽  
Ifn Γ

Background: Recovery from cutaneous leishmaniasis (CL) leads to protection against further lesion development. In contrast, vaccination using killed parasites does not induce enough protection; the reason(s) is not currently known but might be related to different immune response induced against live versus killed parasites. In this study, Th1/Th2 cyto-kine profiles of CL patients were evaluated against live versus killed Leishmania major. Methods: In this study peripheral blood mononuclear cells (PBMC) of the volunteers with active CL lesion (CL), history of CL (HCL) and healthy volunteers were cultured and stimulated with live or killed Leishmania major, the superna-tants were collected and levels of IFN-γ, IL-5 and IL-10 were titrated using ELISA method. Results: The results showed that IFN-γ levels in CL patients (p< 0.001) and HCL volunteers (p< 0.005) are signifi-cantly higher when stimulated with live than stimulated with killed L. major. IFN-γ production in PBMC volunteers with CL and HCL stimulated with live or heat-killed L. major was significantly (p< 0.001) higher than in unstimulated ones. The level of IL-5 in CL patients (p< 0.005) and HCL volunteers (p< 0.001) are significantly lower when stimulated with live than killed L. major. There was no significant difference between the levels of IL-10 in PBMC stimulated with either live or killed L. major. Conclusion: It is concluded that using live Leishmania induces a stronger Th1 type of immune response which justify using leishmanization as a control measure against CL.

scholarly journals CTLA-4 Blockade Enhances the Immune Response Induced by Mycobacterial Infection but Does Not Lead to Increased Protection

1999 ◽  
Vol 67 (8) ◽  
pp. 3786-3792 ◽  
Author(s):  
Joanna Kirman ◽  
Kathy McCoy ◽  
Sarah Hook ◽  
Melanie Prout ◽  
Brett Delahunt ◽  
...  
Keyword(s):  
Immune Response ◽  
Lymph Node ◽  
Cytokine Production ◽  
Mediastinal Lymph Node ◽  
Mycobacterial Infection ◽  
Primary Site ◽  
Draining Lymph Node ◽  
Cell Cytokine Production

ABSTRACT The murine immune response to a pulmonary mycobacterial infection is slow to develop, allowing bacterial numbers to increase in the lung for several weeks after infection. We sought to enhance the protective immune response induced during Mycobacterium bovis BCG infection by administering an antibody that blocks the interaction of CTLA-4 with its ligands, CD80 and CD86. We found that injection of anti-CTLA-4 monoclonal antibody (MAb) greatly enhanced and accelerated the immune response, as measured by increased cellularity of the draining mediastinal lymph nodes, and enhanced antigen-inducible proliferation and gamma interferon production by mediastinal lymphocytes in vitro. However, despite the apparently enhanced immune response in the mediastinal lymph node following treatment with anti-CTLA-4 MAb, there was no improvement in clearance of mycobacteria in the lungs, liver, or spleen. Examination of the primary site of infection, the lung, revealed that CTLA-4 blockade had no effect on the number or function of lymphocytes infiltrating the infected lung tissue. Taken together, these data suggest that in vivo CTLA-4 blockade enhances mycobacterial-infection-induced lymphocyte expansion and effector cell cytokine production in the draining lymph node but does not alter the number or function of lymphocytes at the primary site of infection and therefore does not lead to enhanced clearance of the infection.

scholarly journals Neuroinvasion by Scrapie following Inoculation via the Skin Is Independent of Migratory Langerhans Cells

2005 ◽  
Vol 79 (3) ◽  
pp. 1888-1897 ◽  
Author(s):  
Joanne Mohan ◽  
Moira E. Bruce ◽  
Neil A. Mabbott
Keyword(s):  
Lymph Node ◽  
Langerhans Cells ◽  
Transmissible Spongiform Encephalopathy ◽  
Effective Means ◽  
Infectious Agent ◽  
Spongiform Encephalopathy ◽  
Lymphoid Tissues ◽  
Wild Type ◽  
Draining Lymph Node

ABSTRACT Many natural transmissible spongiform encephalopathy (TSE) infections are likely to be acquired peripherally, and studies in mice show that skin scarification is an effective means of scrapie transmission. After peripheral exposure, TSE agents usually accumulate in lymphoid tissues before spreading to the brain. The mechanisms of TSE transport to lymphoid tissues are not known. Langerhans cells (LCs) reside in the epidermis and migrate to the draining lymph node after encountering antigen. To investigate the potential role of LCs in scrapie transportation from the skin, we utilized mouse models in which their migration was blocked either due to CD40 ligand deficiency (CD40L−/− mice) or after caspase-1 inhibition. We show that the early accumulation of scrapie infectivity in the draining lymph node and subsequent neuroinvasion was not impaired in mice with blocked LC migration. Thus, LCs are not involved in TSE transport from the skin. After intracerebral inoculation with scrapie, wild-type mice and CD40L−/− mice develop clinical disease with similar incubation periods. However, after inoculation via skin scarification CD40L−/− mice develop disease significantly earlier than do wild-type mice. The shorter incubation period in CD40L−/− mice is unexpected and suggests that a CD40L-dependent mechanism is involved in impeding scrapie pathogenesis. In vitro studies demonstrated that LCs have the potential to acquire and degrade protease-resistant prion protein, which is thought to be a component of the infectious agent. Taken together, these data suggest that LCs are not involved in scrapie transport to draining lymphoid tissues but might have the potential to degrade scrapie in the skin.

scholarly journals Immunogenicity Evaluation of a Novel Lentiviral Vaccine Expressing Multi- Epitope Against of Leishmania Major in BALB/c Mice

2020 ◽  
Author(s):  
Mahsa Rabienia ◽  
Zahra Roudbari ◽  
Ali Ghanbariasad ◽  
Abbas Abdollahi ◽  
Alireaza Molazadeh ◽  
...  
Keyword(s):  
Immune Response ◽  
Humoral Immune Response ◽  
Leishmania Major ◽  
Main Group ◽  
Definitive Treatment ◽  
Control Groups ◽  
Epitope Vaccine ◽  
Th1 Response ◽  
Humoral Immune ◽  
Ifn Γ

Abstract Background: Nowadays, the prevention of parasitic diseases including leishmaniasis is one of the health concerns in the world, and cutaneous leishmaniasis is the most common type of these diseases. So far, no drug or vaccine has been approved for definitive treatment of this disease.Methods: In this study, the recombinant lentiviral vaccine containing a new multi-epitope of KMP11 and HASPB of the Leishmania major (L. major) was synthesized that had previously been designed in-silico. The designed multi-epitope was subcloned into the pCDH513 lentiviral vector, and the recombinant lentiviral multi-epitope vaccine (rLV-multi-epitope) was synthesized in the HEK293T cell by the packaging vectors. Also, the Western Blotting method was used to confirm the gene expression. Then, the rLV-multi-epitope vaccine was injected twice, along with two control groups, PBS, and rLV-empty to immunize the BALB /c mice. Twenty-one days after the second injection, the splenocytes of the mice were is­­­­olated and stimulated with the Leishmania lysate.Results: The results of the enzyme-linked immunoassay (ELISA) test not only showed the titer of IFN-γ and IL-4 was increased in the immunized group compared to the controls, but also indicated that the ratio of IFN-γ to IL-4 cytokines in the main group was increased significantly. As a result, the Th1 response was generated in the main group. Moreover, the humoral immune response was assessed and the results showed that the ratio of IgG2a to IgG1 antibody in the sera of the immunized mice was increased compared to the control groups. Also, the ratio of IgG2a to IgG1 was increased in the main group. Therefore, the humoral immune response was increased, which can also have a positive effect on increasing the Th1 response.Conclusions: Our results showed that immunization by the new rLV-multi-epitope vaccine could stimulate the immune system towards the Th1 through increasing the IFN-γ production.

scholarly journals CD4+ Th1 Cells Induced by Dendritic Cell-Based Immunotherapy in Mice Chronically Infected with Leishmania amazonensis Do Not Promote Healing

2004 ◽  
Vol 72 (8) ◽  
pp. 4455-4463 ◽  
Author(s):  
Yannick F. Vanloubbeeck ◽  
Amanda E. Ramer ◽  
Fei Jie ◽  
Douglas E. Jones
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Leishmania Amazonensis ◽  
Interleukin 12 ◽  
Mrna Levels ◽  
Antigen Presenting Cell ◽  
Th1 Response ◽  
Ifn Γ ◽  
Antigen Presenting

ABSTRACT The susceptibility of mice to Leishmania amazonensis infection is thought to result from an inability to develop a Th1 response. Our data show that the low levels of gamma interferon (IFN-γ) produced by the draining lymph node (DLN) cells of chronically infected mice could be enhanced in vitro and in vivo with L. amazonensis antigen-pulsed bone marrow-derived dendritic cells (BM-DC) and the Th1-promoting cytokine interleukin-12 (IL-12). Given intralesionally to chronically infected mice, this treatment induced the upregulation of mRNA levels for IFN-γ, the transcription factor T-box expressed in T cells, and IL-12 receptor β2 in CD4+ T cells from the DLN and an increase in parasite-specific immunoglobulin G2a in the serum. However, this Th1 response was not associated with healing, and the antigen-specific enhancement of IFN-γ production remained impaired in the DLN. However, addition of IL-12 to the in vitro recall response was able to recover this defect, suggesting that antigen-presenting cell-derived IL-12 production may be limited in infected mice. This was supported by the fact that L. amazonensis amastigotes limited the production of IL-12p40 from BM-DC in vitro. Altogether, our data indicate that the immune response of mice chronically infected with L. amazonensis can be enhanced towards a Th1 phenotype but that the presence of Th1 CD4+ T cells does not promote healing. This suggests that the phenotype of the CD4+ T cells may not always be indicative of protection to L. amazonensis infection. Furthermore, our data support growing evidence that antigen-presenting cell function, such as IL-12 production, may limit the immune response in L. amazonensis-infected mice.

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