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 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 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 Mimicry of the a determinant of hepatitis B surface antigen by an antiidiotypic antibody. I. Evaluation in hepatitis B surface antigen responder and nonresponder strains.

1993 ◽  
Vol 177 (1) ◽  
pp. 127-134 ◽  
Author(s):  
M W Pride ◽  
A Thakur ◽  
Y Thanavala
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Lymph Node ◽  
T Cell ◽  
Hepatitis B ◽  
Surface Antigen ◽  
Hepatitis B Surface Antigen ◽  
T Cell Response

B and T cell responses of several strains of mice, immunized with a monoclonal antiidiotype (anti-Id) that mimics the a determinant of hepatitis B surface antigen (HBsAg), were studied to determine if the immune response to the anti-Id was regulated by H-2-linked immune response genes as has been previously observed for HBsAg. We report that immunization with anti-Id could elicit HBsAg-specific antibodies in mice of the H-2d,q, or f haplotype and in an outbred wild mouse strain (Mus spretus), thus circumventing the H-2 haplotype restriction pattern observed when immunizing with HBsAg in H-2f mice. Purified lymph node T cells from mice of the H-2d or q haplotype and M. spretus that were primed in vivo with HBsAg or anti-Id could be stimulated in vitro with either HBsAg or anti-Id but not with an irrelevant antibody of the same subclass as the anti-Id. However, purified lymph node T cells from H-2f mice that were primed in vivo with the anti-Id could only be stimulated in vitro with anti-Id. No in vitro stimulation whatsoever was observed in H-2f mice immunized with HBsAg. The effect of processing and presentation of the anti-Id by antigen-presenting cells (APC) was studied in mice of the H-2d haplotype. Stimulation of purified lymph node T cells by HBsAg and anti-Id was shown to be strictly dependent on APC and restricted by major histocompatibility complex class II antigens at the I-A locus. Treatment of APC with paraformaldehyde or chloroquine abrogated the T cell response to all antigens except for a nine-amino acid synthetic peptide representing a partial analogue of the group a determinant of HBsAg S(139-147). The significance of these results is discussed in the context of understanding the mechanism of mimicry elicited by the anti-Id.

Effect of Shi-Ka-Ron and Chinese Herbs on Cytokine Production of Macrophage in Immunocompromised Mice

1994 ◽  
Vol 22 (03n04) ◽  
pp. 255-266 ◽  
Author(s):  
Rui Jin ◽  
Ling Ling Wan ◽  
Toshimi Mitsuishi ◽  
Shinobu Sato ◽  
Yuki Akuzawa ◽  
...  
Keyword(s):  
Immune Response ◽  
Cytokine Production ◽  
Peritoneal Macrophages ◽  
Chinese Herbs ◽  
Glycyrrhizae Radix ◽  
Crude Extracts ◽  
Immunocompromised Mice ◽  
Tumor Agent

Shi-Ka-Ron is a prescription composed of 8 crude extracts of Chinese herbs. It reduces suppression of cytokine production by peritoneal macrophages in mice Immunocompromised by the anti-tumor agent, cyclophosphamide (CY), in vivo. Although it dose not increase IL-1 production in vitro, it enhances TNF production. We found that Ginseng radix, Lithospermi radix, Astragli radix and Glycyrrhizae radix somewhat reduced suppression of cytokine production in CY treated macrophages. Especially, Glycyrrhizae radix shows an active immune response both in vivo and in vitro. Our results suggested that the mechanism underlying immunomodulation of Shi-Ka-Ron is closely related to cytokine production: each herb stimulating macrophages.

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 The Immunological Enhancement Activity of Propolis Flavonoids LiposomeIn VitroandIn Vivo

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Yang Tao ◽  
Deqing Wang ◽  
Yuanliang Hu ◽  
Yee Huang ◽  
Yun Yu ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Cytokine Production ◽  
Subcutaneous Administration ◽  
Phagocytic Function ◽  
Splenic Lymphocytes ◽  
Adjuvant Activity ◽  
Humoral Immune

The aim of this study was to investigate and assess the effects of propolis flavonoids liposome imposed on the immune system by comparing it to propolis flavonoids and blank liposome.In vitro, the effects of the above drugs on macrophages were assessed by measuring the phagocytic function and cytokine production.In vivo, the immunological adjuvant activity of propolis flavonoids liposome was compared with those of propolis flavonoids and blank liposome. The results showed thatin vitropropolis flavonoids liposome can significantly enhance the phagocytic function of macrophages and the release of IL-1β, IL-6, and IFN-γ. In addition, subcutaneous administration of propolis flavonoids liposome with ovalbumin to mice could effectively activate the cellular and humoral immune response, including inducing higher level concentrations of IgG, IL-4, and IFN-γin serum and the proliferation rates of splenic lymphocytes. These findings provided valuable information regarding the immune modulatory function of propolis flavonoids liposome and indicated the possibility of use of propolis flavonoids liposome as a potential adjuvant.

scholarly journals Trypanosoma cruzi Mexican Strains Differentially Modulate Surface Markers and Cytokine Production in Bone Marrow-Derived Dendritic Cells from C57BL/6 and BALB/c Mice

2019 ◽  
Vol 2019 ◽  
pp. 1-14
Author(s):  
Cecilia Gomes Barbosa ◽  
Tamires Marielem Carvalho Costa ◽  
Chamberttan Souza Desidério ◽  
Paula Tatiana Mutão Ferreira ◽  
Mariana de Oliveira Silva ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Immune Response ◽  
Dendritic Cells ◽  
Trypanosoma Cruzi ◽  
Cytokine Production ◽  
Host Immune Responses ◽  
Mhc Ii ◽  
Mexican Strains

Dendritic cells (DCs) are a type of antigen-presenting cells that play an important role in the immune response against Trypanosoma cruzi, the causative agent of Chagas disease. In vitro and in vivo studies have shown that the modulation of these cells by this parasite can directly affect the innate and acquired immune response of the host in order to facilitate its biological cycle and the spreading of the species. Many studies show the mechanisms by which T. cruzi modulates DCs, but the interaction of these cells with the Mexican strains of T. cruzi such as Ninoa and INC5 has not yet been properly investigated. Here, we evaluated whether Ninoa and INC5 strains evaded the immunity of their hosts by modulating the biology and function of murine DCs. The CL-Brener strain was used as the reference strain. Herein, it was demonstrated that Ninoa was more infective toward bone marrow-derived dendritic cells (BMDCs) than INC5 and CL-Brener strains in both BMDCs of BALB/c and C57BL/6 mice. Mexican strains of T. cruzi induced different cytokine patterns. In BMDCs obtained from BALB/c mice, Ninoa strain led to the reduction in IL-6 and increased IL-10 production, while in C57BL/6 mice Ninoa strain considerably increased the productions of TNF-α and IL-10. Also, Ninoa and INC5 differentially modulated BMDC expressions of MHC-II, TLR2, and TLR4 in both BALB/c and C57BL/6 mice compared to Brazilian strain CL-Brener. These results indicate that T. cruzi Mexican strains differentially infect and modulate MHC-II, toll-like receptors, and cytokine production in DCs obtained from C57BL/6 and BALB/c mice, suggesting that these strains have developed particular modulatory strategies to disrupt DCs and, consequently, the host immune responses.

scholarly journals Antibody Opsonization Enhances Early Interactions between Yersinia pestis and Neutrophils in the Skin and Draining Lymph Node in a Mouse Model of Bubonic Plague

2020 ◽  
Vol 89 (1) ◽  
pp. e00061-20
Author(s):  
Jeffrey G. Shannon ◽  
B. Joseph Hinnebusch
Keyword(s):  
Lymph Node ◽  
Mouse Model ◽  
Yersinia Pestis ◽  
Bubonic Plague ◽  
Content Type ◽  
Vaccine Candidates ◽  
Draining Lymph Node ◽  
Plague Vaccine

ABSTRACTBubonic plague results when Yersinia pestis is deposited in the skin via the bite of an infected flea. Bacteria then traffic to the draining lymph node (dLN) where they replicate to large numbers. Without treatment, this infection can result in highly fatal septicemia. Several plague vaccine candidates are currently at various stages of development, but no licensed vaccine is available in the United States. Though polyclonal and monoclonal antibodies (Ab) can provide complete protection against bubonic plague in animal models, the mechanisms responsible for this antibody-mediated immunity (AMI) to Y. pestis remain poorly understood. Here, we examine the effects of Ab opsonization on Y. pestis interactions with phagocytes in vitro and in vivo. Opsonization of Y. pestis with polyclonal antiserum modestly increased phagocytosis/killing by an oxidative burst of murine neutrophils in vitro. Intravital microscopy (IVM) showed increased association of Ab-opsonized Y. pestis with neutrophils in the dermis in a mouse model of bubonic plague. IVM of popliteal LNs after intradermal (i.d.) injection of bacteria in the footpad revealed increased Y. pestis-neutrophil interactions and increased neutrophil crawling and extravasation in response to Ab-opsonized bacteria. Thus, despite only having a modest effect in in vitro assays, opsonizing Ab had a dramatic effect in vivo on Y. pestis-neutrophil interactions in the dermis and dLN very early after infection. These data shed new light on the importance of neutrophils in AMI to Y. pestis and may provide a new correlate of protection for evaluation of plague vaccine candidates.

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