Probiotics are currently considered as one of tools to modulate immune responses under specific clinical conditions. The purpose of this study was to evaluate whether oral administration of three different probiotics (Lactiplantibacillus plantarum CJLP243, CJW55-10, and CJLP475) could evoke a cell-mediated immunity in immunodeficient mice. Before conducting in vivo experiments, we examined the in vitro potency of these probiotics for macrophage activation. After co-culture with these probiotics, bone marrow derived macrophages (BMDMs) produced significant amounts of proinflammatory cytokines including interleukin-6 (IL-6), IL-12, and tumor necrosis factor-α (TNF-α). Levels of inducible nitric oxide synthase (inos) and co-stimulatory molecules (CD80 and CD86) were also upregulated in BMDMs after treatment with some of these probiotics. To establish an immunocompromised animal model, we intraperitoneally injected mice with cyclophosphamide on day 0 and again on day 2. Starting day 3, we orally administered probiotics every day for the last 15 d. After sacrificing experimental mice on day 18, splenocytes were isolated and co-cultured with these probiotics for 3 d to measure levels of several cytokines and immune cell proliferation. Results clearly indicated that the consumption of all three probiotic strains promoted secretion of interferon-γ (IFN-γ), IL-1β, IL-6, IL-12, and TNF-α. NK cell cytotoxicity and proliferation of immune cells were also increased. Taken together, our data strongly suggest that consumption of some probiotics might induce cell-mediated immune responses in immunocompromised mice.
The immunosuppressive activity of the Methanol extract of bark of Madhuca longifolia (Koenig) consisting of a mixture of saponins, flavonoids, tannins, steroids, phenol and glycosides was studied on the immune responses in mice. Methanol extract of Madhuca longifolia (MLL) was administered orally at doses of 50, 100 and 150 mg/kg/day to healthy mice divided into four groups consisting of six animals each. The assessment of immunomodulatory activity was carried out by testing the humoral (antibody titre) and cellular (foot pad swelling) immune responses to the antigenic challenge by sheep RBCs. Furthermore, the effect on hematological parameters as well as relative organ weight was determined. On oral administration MML showed a significant decrease delayed type hypersensitivity (DTH) response whereas the humoral response to sheep RBCs was unaffected. Thus MLL significantly suppressed the cellular immunity by decreasing the footpad thickness response to sheep RBCs in sensitized mice. With a dose of 100 and 150 mg/kg/day the DTH response was $7.66{\pm}2.75$ and $6.41{\pm}1.21$ respectively in comparison to corresponding value of $14.50{\pm}2.38$ for untreated control group. These differences in DTH response were statistically significant (P < 0.05). The study demonstrates that MLL shows preferential suppression of the components of cell-mediated immunity and shows no effect on the humoral immunity.
Khalaf, Abd EI-Azeim A.;Morgan, Ashraf M.;Mekawy, Mohey M.;Ali, Maged F.
Toxicological Research
/
v.24
no.1
/
pp.51-58
/
2008
The present study was designed to explore the immunotoxic effects of orally administered aluminum (AI) on pregnant rats (n = 60) and their growing fetuses and consequently on the animal wealth. The animals were randomly allocated into three equal groups of 20 rats each. The first group has no treatment and kept as a control (G1). The second and third groups of pregnant rats were treated orally with aluminum chloride at 345 mg/Kg b.wt. The second group (G2) received the tested compound from the $6^{th}$ day of gestation to the end of weaning, whereas the third group (G3) received the tested compound from the $15^{th}$h day of gestation to the end of weaning. Control and treated animals (dams and offspring) were immunized ip with (0.5 ml) 20% sheep red blood cell (SRBC) suspension seven days before the end of experiments. At the end of exposure, ten dams and ten offspring from each group were used for assessment of cell-mediated immunity and a similar number of animals were sacrificed for evaluating the humoral immune response and serum protein profile. Aluminum chloride exposure of dams ($G_2&G_3$) caused significant suppression of both cell mediated and humoral immune responses in the obtained offsprings compared to the control group ($G_1$) without any significant effect on the immune responses of these dams. Moreover, the serum total globulins, albumin/ globulin (A/G) ratio and gamma globulin fraction were significantly decreased in the treated dam's offsprings compared to the corresponding controls while the serum total protein and all serum protein fractions showed non significant difference between the control and treated dams and between the two treated dam groups themselves. There were no histopathological changes observed in thymus, spleen and liver of the control and treated dams. Thymus of treated dam's offsprings (G2) showed lymphoid depletion in both cortex and medulla. Their spleens showed lymphoid depletion in the white pulps and congestion with hemosiderosis in the red pulps. Liver of treated dam's offsprings showed dilation and congestion of its central vein with degenerative changes in the hepatocytes. These histopathological changes were more severe in G2 than in G3 offsprings. It can be concluded that gestational and/ or lactation exposure of pregnant dams to AI chloride caused suppression of both cellular and humoral immune responses of their offsprings.
The response of broiler chicks to intubation of nutrients (starch, casein, soybean oil or their combinations) into the crop immediately after hatch was evaluated for performance, intestinal development, meat yield and immune competence up to 35 d of age. A control group with no access to feed and two test groups fed either inert material (sawdust) or starter diet for the initial 24 h after hatch were compared with nutrient intubated groups (n = 7). A total of 300 broiler chicks were equally distributed to 10 dietary groups with 6 replicates of 5 chicks each. After 24 h of hatch, all groups were fed ad libitum the starter (0-21 d) and finisher diets (22-35 d). Results indicated that post-hatch intubation of starch into the crop significantly (p${\leq}$0.05) improved body weight (at 14 and 35 d of age), readyto-cook meat yields, weights of breast muscle and small intestine segments, cell-mediated immune response, ND titers and weight of bursa compared to chicks starved or fed sawdust during the initial 24 h after hatch. However, chicks with access to feed immediately after hatch or intubation of starch, soybean oil, starch+casein, starch+soybean oil or starch+casein+soybean oil exhibited similar positive effects. Intubation of casein either alone or in combination with soybean oil was superior to the starved or sawdust fed groups, but inferior to other groups for all the parameters studied. It was concluded from the study that intubation of starch individually or in combination with casein and/or soybean oil effectively circumvented the negative effects of post-hatch starvation for 24 h. Among the nutrients intubated, carbohydrate (starch) was better utilized by the chicks than protein (casein) or fat during the initial post-hatch period.
Kang, Jung Won;Shin, Hyeon Yeong;Oqani, Reza K.;Lin, Tao;Lee, Jae Eun;Kim, So Yeon;Lee, Joo Bin;Jin, Dong Il
Reproductive and Developmental Biology
/
v.41
no.3
/
pp.57-63
/
2017
Xenotransplantation is proposed as a solution to the problem of organ shortage. However, transplantation of xenogeneic organs induces an antigen-antibody reaction in ${\alpha}$-1,3-gal structure that are not present in humans and primates, and thus complement is also activated and organs die within minutes or hours. In this study, we used FasL gene, which is involved in the immune response of NK cell, and US11, which suppresses MHC Class I cell membrane surface expression, to inhibit cell mediated rejection in the interspecific immunity rejection, and also hDAF(CD55) was introduced to confirm the response to C3 complement. These genes were tranfeced into Korean native pig fetal fibroblasts using pCAGGS vector. And cytotoxicity of NK cell and human complement was confirmed in each cell line. The US11 inhibited the cytotoxicity of NK cell and, in addition, the simultaneous expression of US11 and Fas ligand showed excellent suppress to T-lymphocyte cytotoxicity, hDAF showed weak resistance to cytotoxicity of natural killer cell but not in CD8+ CTLs. Cytotoxicity study with human complement showed that hDAF was effective for reducing complement reaction. In this studies have demonstrated that each gene is effective in reducing immune rejection.
An experiment was conducted on crossbred male calves to study the effect of arsenic (As) on immunity status and certain hematological parameters. Ten crossbred male calves of 3-4 months of age were distributed into two equal groups. Group I was kept as control, whereas, group II was supplemented daily with 50 ppm As (as $As_sO_3$) up to 90 days, in the diet. Calves of both groups were fed as per ICAR standards and their requirements were fulfilled by feeding concentrate mixture and green oats. All calves were kept under similar managemental conditions. Blood samples were collected at fortnightly intervals to estimate various haematological parameters and superoxide dismutase (SOD) enzyme activity. Serum Ig and serum glutamic pyruvate transaminase (SGPT) were also measured. Cell-mediated immune responses of the calves were monitored at 0, 45 and 90 of experimental feeding, through lymphocyte proliferation. No change in blood total leukocyte counts (TLC), differential leukocyte counts (DLC), packed cell volume (PCV), haemoglobin (Hb) and SGPT was observed with As supplementation. A decrease in SOD activity was noticed in group II calves. Stimulation index (SI) for lymphocyte proliferation decreased from 1.14 to 0.79 in group II calves during 90 days experimental feeding, whereas, there was no change in SI values in group I indicating significant decrease in immune response of As supplemented calves. Blood As concentration increased in group II calves with the decrease in immune response. Short term supplementation of As to growing calves suggested suppressive effects on cell-mediated immunity. However, long term experiments are required to demonstrate clearly the efects of this toxic metal in calves.
Kirthika, Perumalraja;Park, Sungwoo;Jawalagatti, Vijayakumar;Lee, John Hwa
Journal of Veterinary Science
/
v.23
no.3
/
pp.41.1-41.15
/
2022
Background: Proliferative enteritis caused by Lawsonia intracellularis undermines the economic stability of the swine industry worldwide. The development of cost-effective animal models to study the pathophysiology of the disease will help develop strategies to counter this bacterium. Objectives: This study focused on establishing a model of gastrointestinal (GI) infection of L. intracellularis in C57BL/6 mice to evaluate the disease progression and lesions of proliferative enteropathy (PE) in murine GI tissue. Methods: We assessed the murine mucosal and cell-mediated immune responses generated in response to inoculation with L. intracellularis. Results: The mice developed characteristic lesions of the disease and shed L. intracellularis in the feces following oral inoculation with 5 × 107 bacteria. An increase in L. intracellularis 16s rRNA and groEL copies in the intestine of infected mice indicated intestinal dissemination of the bacteria. The C57BL/6 mice appeared capable of modulating humoral and cell-mediated immune responses to L. intracellularis infection. Notably, the expression of genes for the vitamin B12 receptor and for secreted and membrane-bound mucins were downregulated in L. intracellularis -infected mice. Furthermore, L. intracellularis colonization of the mouse intestine was confirmed by the immunohistochemistry and western blot analyses. Conclusions: This is the first study demonstrating the contributions of bacterial chaperonin and host nutrient genes to PE using an immunocompetent mouse model. This mouse infection model may serve as a platform from which to study L. intracellularis infection and develop potential vaccination and therapeutic strategies to treat PE.
Kim, Joung-Hoon;Kim, In-Hoon;Chae, Byeong-Suk;Kang, Tae-Wook;Park, Chan-Bong;Ahn, Young-Keun
YAKHAK HOEJI
/
v.40
no.2
/
pp.230-237
/
1996
The fractions of Epimedii Herba were examined for the immunological effects in ICR mice. Mice were divided into 4 groups and administered orally the fractions of Epimedii Herba for 10 days. The results of this study were summarized as following: (1) The fraction 1 (EtOAc layer) administered group as compared with control group significantly decreased spleen weight, Arthus reaction and hemagglutination (HA) titer but significantly increased circulating white blood cells (WBC). (2) The fraction 2 ($H_20$ layer) administered group as compared with control group significantly decreased liver weight, Arthus reaction and HA titer but significantly increased WBC. (3) The fraction 3 (ppt) administered group as compared with control group significantly increased liver weight, thymus weight rate, delayed type hypersensitivity, phagocytic activity and WBC. The results showed that Frs. 1 and 2 administered groups reduced humoral immune response but increased WBC, and that Fr. 3 administered group increased cell-mediated immune response, phagocytic activity and WBC.
Kim, Joong-Gon;Lee, Soo-Hyun;Lee, Jae-Woo;B.S. Kwon;Kang, Chang-Yuil
Proceedings of the Korean Society of Applied Pharmacology
/
1995.04a
/
pp.82-82
/
1995
4-lBB molecule is expressed on the surface of activated CD4$\^$+/ and CD8$\^$+/ T cells. We generated a panel of anti-4-1 B5 murine mAbs using a fusion protein consisting of the extracellular domain of human 4-1 BB fused to Glutathione S-transferase. The binding activity against cell surface 4-1 BB molecule was assessed by flow cytometry analysis. These studies showed that several anti-4-1 BB mAbs bound to 10-30% of CD4$\^$+/ and CD8$\^$+/T cells in PHA or Con A stimulated PBLs, although these mAbs interacted with only, l-2% of CD4$\^$+/ and CD8$\^$+/ T cells in normal PBLs, indicating the specificity of mAbs to the 4-l BB molecule on activated CD4$\^$+/ and CD8$\^$+/ T cells. Next, we examined the effect of an anti-4-l BB mAb (4B4-1-1) on allogeneic mixed lymphocyte reactions (MLRs). The data indicated that the antibody significantly inhibited the proliferative response at higher concentrations. When tested with several T cell mitogens, the antibody had no stimulatory or inhibitory effects on the mitogen-mediated T cell proliferation. These data suggest that 4-1 BB molecule may play a role in the regulation of antigen-mediated immune response.
Nu Z. N. Nguyen;Vuvi G. Tran;Saerom Lee;Minji Kim;Sang W. Kang;Juyang Kim;Hye J. Kim;Jong S. Lee;Hong R. Cho;Byungsuk Kwon
IMMUNE NETWORK
/
v.20
no.6
/
pp.49.1-49.15
/
2020
C-C chemokine receptor type 5 (CCR5) regulates the trafficking of various immune cells to sites of infection. In this study, we showed that expression of CCR5 and its ligands was rapidly increased in the kidney after systemic Candida albicans infection, and infected CCR5-/- mice exhibited increased mortality and morbidity, indicating that CCR5 contributes to an effective defense mechanism against systemic C. albicans infection. The susceptibility of CCR5-/- mice to C. albicans infection was due to impaired fungal clearance, which in turn resulted in exacerbated renal inflammation and damage. CCR5-mediated recruitment of NK cells to the kidney in response to C. albicans infection was necessary for the anti-microbial activity of neutrophils, the main fungicidal effector cells. Mechanistically, C. albicans induced expression of IL-23 by CD11c+ dendritic cells (DCs). IL-23 in turn augmented the fungicidal activity of neutrophils through GM-CSF production by NK cells. As GM-CSF potentiated production of IL-23 in response to C. albicans, a positive feedback loop formed between NK cells and DCs seemed to function as an amplification point for host defense. Taken together, our results suggest that CCR5-mediated recruitment of NK cells to the site of fungal infection is an important step that underlies innate resistance to systemic C. albicans infection.
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