Serum IgM Titers Research Articles

Glucose dependent resistance associated with intestinal microbiota facilitate teleost to survive bacterial infection

Host microbiota interaction affects the metabolism and immune regulation in the host. To explore the disease resistance mechanism and the host-microbiota interaction details, the intestinal transcriptome and microbiome of moribund and surviving fish infected with Aerompnas hydrophila as well as healthy controls were cross-analyzed. Survivors presented an intestinal microbiome with slight change and more intensive interspecies cooperation, while a distinct gene expression profile related to glycometabolism and immunomodulation was observed, resulting in lower-level inflammation in intestinal tissue. Genes related to FoxO, Insulin, and Glucagon signaling pathways, such as g6pc, socs2, and foxg1, correlated positively with intestinal Eubacterium_coprostanoligenes_Group, Mannheimia, Leptotrichia, and Shewanella, corresponding to a higher serum glucose level and IgM titer in surviving fish. Besides, Pseudomonas and Shewanella, with higher abundance in surviving fish, showed antagonism towards the pathogen in vitro, and a positive correlation with serum glucose level and IgM titer, respectively. Co-cultures promoted these antagonism effects and these effects connected with glucose concentration. Glucose supplementation to fish raised the survival rate significantly. In general, glycometabolism homeostasis is critical for fish to survive A. hydrophila infection. Metabolism modulation would be a potential approach to facilitate bacterial infection resistance.

The effect of a web-based lifestyle intervention on nutritional status and physical activity on prevention of COVID-19: a randomized controlled trial in women's empowerment.

Healthy dietary intake and physical activity affect the immune systems. The present study aimed to investigate the effects of a web-based lifestyle intervention on nutritional status, physical activity, and prevention of COVID-19. Three hundred-three women (30-60 years old), who did not have COVID-19 in the City of Ardabil, participated in this study. Participants were randomized into an intervention (n = 152) or control group (n = 151). The intervention group received eight online educational sessions focusing on a healthy diet and physical activity via the website. There was no educational session for the control group during the intervention, but they were placed on the waiting list to receive the intervention and given access to the website and educational content after the follow-up. Outcomes were nutritional status, physical activity, immunoglobulin G (IgG), and immunoglobulin M (Ig M) antibody titers against the virus. They were evaluated at the baseline, after 4 and 12 weeks. Significant improvements in weight (P < 0.001), BMI (P < 0.001), total energy (P = 0.006), carbohydrate (P = 0.001), protein (P = 0.001), and fat (P < 0.001) were found for the intervention group compared to the control group during the study. MET-min/week for moderate physical activity increased during the time for the intervention and control groups (P < 0.001 and P = 0.007, respectively). MET-min/week for walking activity rose in the post-intervention and follow-up compared to that in the baseline in the groups (P < 0.001 for both groups). Total physical activity was increased during the study (P < 0.001) for both groups. The mean of serum IgG and IgM titers against the virus were increased during the study in both groups in time effect (P < 0.001). There was a significant time x group interaction for carbohydrate and fat intakes (P = 0.005 and P = 0.004, respectively). The web-based lifestyle intervention may improve nutritional status and physical activity, and have the potential to reduce the risk of contracting a COVID-19 infection.

Expression kinetics of cytokines and the humoral antibody response concerning short-term protection induced by radiation-attenuated Trypanosoma evansi in bovine calves.

'Surra', an economically important disease of livestock, is caused by the parasitic blood protozoon Trypanosoma evansi. Both innate and adaptive immunity contribute to the protection against this infection. T-helper cells play a crucial role in the antibody-mediated clearance of T. evansi. We present here the data on the kinetics of expression of important Th1, Th2 and Th17 cytokines, vis-a-vis the dynamics of humoral response in bovine calves following immunization with γ-radiation-attenuated live T. evansi and later challenged with homologous virulent T. evansi. Significant upregulation of the pro-inflammatory Th1 and Th17 cytokines was correlated with the IgG2-mediated protection in the immunized bovine calves post-challenge. The calves were immunized with 5×106 500Gy γ-radiation-attenuated live T. evansi (horse isolate) thrice at 15days intervals through the subcutaneous route and subsequently, challenged with 1×103 virulent T. evansi on day 50. Significantly high serum IgG (1:1600) and IgM (1:800) titres were recorded on week 2 PC, whereas the peak serum IgG2 titre (1:800) was recorded on week 6 PC. Significant upregulation of IFN-γ, TNF, IL-1β, and IL-2 was recorded between days 1 to 3 PC, while the same for IL-17 was recorded on day 14 PC. The immunized calves were free from parasitemia post-challenge and were clinically healthy till the end of the experiment. Significant upregulation of IL-10 and IL-4 transcripts and a corresponding increase of serum IgG1 titre in the placebo group helped patency of the parasite in an anti-inflammatory environment and clinical exacerbation of the disease. The expression of the important Th1 cytokines was crucial for antibody-mediated short-term protection against a lethal challenge of T. evansi in cattle.

Inhibitory effect of concomitantly administered rabies immunoglobulins on the immunogenicity of commercial and candidate human rabies vaccines in hamsters

The World Health Organization protocol for rabies post-exposure prophylaxis (PEP) recommends extensive wound washing, immediate vaccination, and administration of rabies immunoglobulin (RIG) in severe category III exposures. Some studies have shown that RIG can interfere with rabies vaccine immunogenicity to some extent. We investigated the interference of RIG on a next generation highly purified Vero cell rabies vaccine candidate (PVRV-NG) versus standard-of-care vaccines in a previously described hamster model. The interference of either human (h) or equine (e) RIG on the immune response elicited by PVRV-NG, Verorab® (purified Vero cell rabies vaccine, PVRV), and Imovax® Rabies (human diploid cell rabies vaccine; HDCV) was evaluated using the 4-dose Essen PEP regimen. The anti-rabies seroneutralizing titers and specific serum IgM titers were measured by fluorescent antibody virus neutralization test and enzyme-linked immunosorbent assay, respectively, for the vaccines administered with or without RIG. The RIG interference on PVRV-NG, observed transiently at Day 7, was similar to that on PVRV and tended to be lower than that on HDCV using both read-outs. In summary, the results generated in the hamster model showed that RIG induced similar or less interference on PVRV-NG than the standard-of-care vaccines.

In ovo co-administration of vitamins (A and D) and probiotic lactobacilli modulates immune responses in broiler chickens

There is evidence that probiotic lactobacilli, in addition to essential vitamins, such as vitamin A and D, have immunomodulatory properties that enhance immune response of neonatal chickens against infections. The present study evaluated the effects of in ovo administration of retinoic acid (RA), 25-Hydroxyvitamin D3 (VitD), and a lactobacilli cocktail on cytokine gene expression, antibody responses and spleen cell subsets in chickens. RA (90 µmol/egg) and VitD (0.6 μg/egg) were administered in ovo, either alone or in combination with lactobacilli (107 CFU/egg), at embryonic d 18. On d 5 and 10 posthatch, gene expression and cellular composition were analyzed in the bursa of Fabricius and spleen. Birds were immunized on d 14 and 21 posthatch with 2 T-dependent antigens, sheep red blood cells (SRBC) and keyhole limpet hemocyanin (KLH), to assess their antibody responses. Sera were collected from the immunized chickens on d 14, 21, 28, and 35 posthatch. The results demonstrated that lactobacilli treatment increased the number of monocyte/macrophages (KUL01+) and CD3+CD4+ T cells in the spleen, and enhanced serum anti-KLH IgM and IgY on d 14 postprimary immunization (P < 0.05). RA significantly increased serum IgY and IgM titers to KLH and enhanced the expression of interferon (IFN)-α, interleukin (IL)-1β, IL-6, IL-8, IL-12, IL-13, and transforming growth factor-β (TGF-β) in the bursa of Fabricius (P < 0.05). The percentage of CD3+CD8+ T cells, and monocyte/macrophages (KUL01+) was elevated in the spleen as well (P < 0.05). These findings reveal that prehatch administration of RA improves immunocompetency of neonatal chickens by increasing the production of cytokines that regulate innate immunity and through enhancing antibody-mediated response against T-dependent antigens.

Long-term efficacy of nasal vaccination against enteric red mouth (ERM) disease and infectious hematopoietic necrosis (IHN) in juvenile rainbow trout (Oncorhynchus mykiss)

Previous research demonstrated that bacterial and viral vaccines delivered via the nasal route in rainbow trout (Oncorhynchus mykiss) at 7 and 28 days post-vaccination are highly protective (>95% protection). Long-term protection following nasal vaccination in teleosts has not been evaluated. The goal of this study was to assess efficacy and immune responses at 6 months (mo) post-vaccination (mpv), and long-lasting immune responses at 12 mpv of two different vaccines: an inactivated enteric red mouth disease (ERM) Yersinia ruckeri bacterin and a live attenuated infectious hematopoietic necrosis virus (IHNV) vaccine. Juvenile rainbow trout were vaccinated for Y. ruckeri via intraperitoneal (I.P.) and intranasal (I.N.) routes, and for IHNV by intramuscular (I.M.) and I.N. routes, then challenged at 6 mpv. Immune responses were determined at 6 and 12 mpv. ERM vaccine I.P. delivery elicited significantly higher serum IgM-specific titers that remained elevated compared to mock-vaccinated fish at 6 mpv. By 12 mpv, antibody titers to Y. ruckeri were not significantly different across all treatments. Following Y. ruckeri challenge at 6 mpv, a significant difference in cumulative percent mortality (CPM) was found for I.P.-vaccinated fish but not I.N.-vaccinated fish. I.M. and I.N. vaccination with live attenuated IHNV did not result in significant specific serum IgM titers at 6 or 12 mpv. Yet, I.N.-vaccinated fish showed the lowest CPM 6 mpv indicating long-term protection that does not correlate with systemic IgM responses. Repertoire analyses confirmed unique expansions of VH-JH rearrangements in the spleen of rainbow trout 12 mpv that varied with the type of vaccine and route of vaccination. Combined, these data demonstrate that I.N. vaccination with a live attenuated viral vaccine confers long lasting protection, but I.N. ERM vaccination does not and booster before 6 mpv is recommended.

Adjunctive IgM-enriched immunoglobulin therapy with a personalised dose based on serum IgM-titres versus standard dose in the treatment of septic shock: a randomised controlled trial (IgM-fat trial)

IntroductionIn patients with septic shock, low levels of circulating immunoglobulins are common and their kinetics appear to be related to clinical outcome. The pivotal role of immunoglobulins in the host...

B-Cell-Specific Myd88 L252P Expression Causes a Premalignant Gammopathy Resembling IgM MGUS.

A highly recurrent somatic L265P mutation in the TIR domain of the signaling adapter MYD88 constitutively activates NF-κB. It occurs in nearly all human patients with Waldenström’s macroglobulinemia (WM), a B cell malignancy caused by IgM-expressing cells. Here, we introduced an inducible leucine to proline point mutation into the mouse Myd88 locus, at the orthologous position L252P. When the mutation was introduced early during B cell development, B cells developed normally. However, IgM-expressing plasma cells accumulated with age in spleen and bone, leading to more than 20-fold elevated serum IgM titers. When introduced into germinal center B cells in the context of an immunization, the Myd88L252P mutation caused prolonged persistence of antigen-specific serum IgM and elevated numbers of antigen-specific IgM plasma cells. Myd88L252P-expressing B cells switched normally, but plasma cells expressing other immunoglobulin isotypes did not increase in numbers, implying that IgM expression may be required for the observed cellular expansion. In order to test whether the Myd88L252P mutation can cause clonal expansions, we introduced it into a small fraction of CD19-positive B cells. In this scenario, five out of five mice developed monoclonal IgM serum paraproteins accompanied by an expansion of clonally related plasma cells that expressed mostly hypermutated VDJ regions. Taken together, our data suggest that the Myd88L252P mutation is sufficient to promote aberrant survival and expansion of IgM-expressing plasma cells which in turn can cause IgM monoclonal gammopathy of undetermined significance (MGUS), the premalignant condition that precedes WM.

Serum IgM against SARS-CoV-2 correlates with in-hospital mortality in severe/critical patients with COVID-19 in Wuhan, China.

Severe/critical patients with coronavirus disease 2019 (COVID-19) have become the central issue in the current global pandemic due to their high mortality rate. However, the relationship between antibody response and clinical outcomes has not been well described in this group. We conducted a single-center, retrospective, cohort study to investigate the relationship between serum immunoglobulin G (IgG) and IgM and clinical outcomes in severe/critical patients with COVID-19. Seventy-nine severe/critical patients with COVID-19 admitted in Wuhan Asia General Hospital in Wuhan, China during January 22, 2020 to March 6, 2020 were included. Serum antibodies were measured at day 25 (SD, 7) post illness onset. The median IgG titer was 113 (IQR 81-167) AU/ml, and IgM titer was 50 (IQR, 23-105) AU/ml. Patients whose IgM titer ≥ 50 AU/ml had higher in-hospital mortality (p=0.026). IgM titer ≥ 50 AU/ml was also correlated with higher incidences of Acute Respiratory Distress Syndrome (ARDS) and sepsis shock. Antibody remeasurements were performed in 42 patients, where IgM titer declined significantly in survivors (p=0.031). Serum IgM titer changes according to the COVID-19 progression. The severe/critical patients with COVID-19 have a higher risk of clinical adverse events when IgM titer ≥ 50 AU/ml. Further decreasing of IgM could imply a better outcome in severe/critical cases.

Efficacy of live attenuated vaccine derived from the Streptococcus agalactiae on the immune responses of Oreochromis niloticus

Streptococcus agalactiae species have been recognized as the main pathogen causing high mortality in fish leading to significant worldwide economical losses to the aquaculture industries. Vaccine development has become a priority in combating multidrug resistance in bacteria; however, there is a lack of commercial live attenuated vaccine (LAV) against S. agalactiae in Malaysia. The aim of this study is to compare two methods using attenuated bacteria as live vaccine and to evaluate the efficacy of selected LAV on the immune responses and resistance of Oreochromis niloticus (tilapia) against S. agalactiae. The LAV derived from S. agalactiae had been weakened using the chemical agent Acriflavine dye (LAV1), whereas the second vaccine was weakened using serial passages of bacteria on broth media (LAV2). Initial immunization was carried out only on day one, given twice-in the morning and evening, for the 42 day period. Serum samples were collected to determine the systemic antibody (IgM) responses and lysozymal (LSZ) activity using ELISA. On day 43 after immunization, the fish were injected intraperitoneally (i.p) with 0.1 mL of S. agalactiae at LD50 = 1.5 × 105 (CFU)/fish. Fish were monitored daily for 10 days. Clinical signs, mortality and the relative percent of survival (RPS) were recorded. Trial 1 results showed a significant increased (P < 0.05) in serum IgM titers and LSZ activity as compared to LAV2 and the control group (unvaccinated fish). The efficacy of LAV1 was proven effective as determined by the RPS values, LAV1 at 81.58% as compared to LAV2 at 65.79%. Trial 2 of LAV1 and control group were further determined by administering primary and booster doses revealed a RPS value for LAV1 of 82.05%, with the significant enhancement on the immune responses of tilapia as compared to control group. In conclusion, LAV revealed to elevate antibody IgM levels, LSZ activity and provide long-term protection when added to feed. LAV is a low-cost vaccine shown to rapidly increase the immune response of fish and increase survival rates of fish against S. agalactiae infection.

Differential Modulation of IgT and IgM upon Parasitic, Bacterial, Viral, and Dietary Challenges in a Perciform Fish.

Three different immunoglobulin (Ig) isotypes can be found in teleost fish, IgM, IgD, and the teleost-specific IgT. IgM is considered to have a systemic activity, and IgT is attributed a mucosal role, similar to mammalian IgA. In this study, the complete sequence of gilthead sea bream IgM and IgT in their membrane (m) and soluble (s) forms are described for the first time in a perciform fish. Their constitutive gene expression is analyzed in different tissues, and their regulation upon viral, bacterial, parasitic, mucosal vaccination and dietary challenges are studied. GCB IgM and IgT have the prototypical structure when compared to other fish Igs. The constitutive expression of sIgM was the highest overall in all tissues, whereas mIgT expression was highest in mucosal tissues, such as gills and intestine. IgM and IgT were differentially regulated upon infection. IgT was highly upregulated locally upon infection with the intestinal parasite Enteromyxum leei or systemically after Nodavirus infection. Long-term intestinal parasitic infections increased the serum titer of both isotypes. Mucosal vaccination against Photobacterium damselae subsp. piscicida finely regulated the Ig response inducing a systemic increase of IgM titers in serum and a local IgT response in skin mucus when animals were exposed to the pathogen by bath challenge. Interestingly, plant-based diets inhibit IgT upregulation upon intestinal parasitic challenge, which was related to a worse disease outcome. All these results corroborate the mucosal role of IgT and emphasize the importance of a finely tuned regulation of Ig isotypes upon infection, which could be of special interest in vaccination studies.

X chromosome gene Ddx3x is involved in B-cell development

Abstract Ddx3x, located on the X chromosome, belongs to the DEAD box RNA helicase family. Ddx3x is previously implicated in RNA metabolism, cell cycle control, apoptosis, tumorigeneses and viral infections. In the process of exploring the role of ddx3x in the female predominance of systemic lupus erythematosus, we found abnormalities in B-cell development within conditional ddx3x-deficient mice. Breeding of ddx3x-floxed mice with Vav1-Cre mice led to deletion of ddx3x in hematopoietic cells (Vav1ddx3x). Ddx3x expression was reduced 80% in the bone marrow (BM) of Vav1ddx3x mice. Hematopoietic deficiency of ddx3x is associated with a reduced proportion and absolute number of B cells, starting at the small pre-B cell stage, and then subsequently immature B cells and mature B cells in bone marrow, relative to wild-type mice. In spleen, the frequency and number of follicular B cells (FOB) were significantly decreased whereas the numbers of marginal zone, germinal center and plasma-blast B cells were sustained. Mixed Vav1ddx3x and wild-type bone marrow chimera mice demonstrated a B-cell intrinsic effect. Surprisingly, despite fewer B cells in the BM and spleen, serum IgM, IgA and IgG titers were elevated in Vav1ddx3x mice, suggesting ddx3x may affect B-cell function as well. In conclusion, we showed that ddx3x deficiency affects B-cell development resulting in a loss of B cells in bone marrow and the periphery and an increase in serum immunoglobulin levels.

Comprehensive Mechanism Analysis of Mesoporous-Silica-Nanoparticle-Induced Cancer Immunotherapy.

A plain mesoporous silica nanoparticle without any immunomodulatory molecules significantly enhances anticancer immunity in vivo. Comprehensive mechanism of mesoporous-silica-nanoparticle-induced cancer immunotherapy is analyzed in this paper. The mesoporous silica nanoparticle promotes both Th1 and Th2 immune responses, as it accelerates lymphocytes proliferation, stimulates IFN-γ, IL-2, IL-4, and IL-10 cytokine secretion by lymphocytes ex vivo, and increases IgG, IgG1, IgG2a, IgM, and IgA antibody titers in mice serum compared with those of alum and adjuvant-free groups. Moreover, the mesoporous silica nanoparticle enhances effector memory CD4(+) and CD8(+) T cell populations in three most important immune organs (bone marrow, lymph node, and spleen) of mice compared with those of alum and adjuvant-free groups three months after adjuvant injection. The present study paves the way for the application of mesoporous silica nanoparticle as immunoadjuvant for cancer immunotherapy.

A Retrospective Analysis of 7 Human Immunodeficiency Virus-Negative Infants Infected by Penicillium marneffei.

Infection with Penicillium marneffei has rarely been reported in human immunodeficiency virus (HIV)-negative infants. We aimed to determine the epidemiological, clinical, pathological, and immunological characteristics of 7 HIV-negative infants infected by P. marneffei, and to provide insights into its diagnosis and treatment.We retrospectively reviewed the cases of 7 HIV-negative infants infected by P. marneffei who presented to the First Affiliated Hospital of Guangxi Medical University between January 1, 2003 and December 1, 2014. The infants’ median age was 23.43 months (SD = 8.34), and all lived in Guangxi Province in China, where P. marneffei is endemic. The median time from disease onset to diagnosis was 2.29 months (SD = 2.12). Of the cases studied, 5 (71.43%) had medical histories that included frequent pneumonia or bronchopneumonia, thrush, congenital megacolon, glucose-6-phosphate dehydrogenase deficiency, and hemophagocytic syndrome. The most common symptoms were fever, cough, and anemia, followed by lymphadenopathy, hepatosplenomegaly, and being underweight. Four patients had slightly elevated white blood cell counts. The lymphocyte and CD4+ T-cell counts were normal. The CD8+ T-cell counts, serum immunoglobulin (Ig) G titer, and serum IgA titer were low in 5 patients, and the serum IgM titers were high in 3 infants. Caseous necrosis was observed in 3 patients whose lymph nodes were affected. One case who received intravenous amphotericin B and 3 cases who received intravenous voriconazole improved, and these patients were cured after continual treatment with oral voriconazole for 6 or 12 months. The remaining patients died before they received antifungal treatment.P. marneffei causes severe disease and disseminated infections, and it has high mortality rates in HIV-negative infants in endemic areas. P. marneffei susceptibility may be associated with immunodeficiencies or immune disorders. In endemic areas, clinicians should aware of disseminated P. marneffei infections when infants present with serious or recurrent infections, even if they are HIV negative. P. marneffei is highly susceptible to amphotericin B and voriconazole. Timely diagnosis and treatment can improve patients’ prognoses. Intravenous voriconazole could be recommended as the initial antifungal agent for HIV-negative infants infected by P. marneffei, because of its low nephrotoxicity, high sensitivity, and high efficacy levels.

Dietary rice bran protects against rotavirus diarrhea and promotes Th1-type immune responses to human rotavirus vaccine in gnotobiotic pigs.

Rice bran (RB) contains a distinct stoichiometry of phytochemicals that can promote gut mucosal immune responses against enteric pathogens. The effects of RB on rotavirus diarrhea and immunogenicity of an attenuated human rotavirus (HRV) vaccine were evaluated in gnotobiotic pigs. The four treatment groups studied were RB plus vaccine, vaccine only, RB only, and mock control. Pigs in the RB groups were fed the amount of RB that replaced 10% of the pigs' total daily calorie intake from milk starting from 5 days of age until they were euthanized. Pigs in the vaccine groups were orally inoculated with two doses of the attenuated HRV vaccine. A subset of pigs from each group was orally challenged with the homologous virulent HRV on postinoculation day 28. Diarrhea and virus shedding were monitored daily from postchallenge day 0 to day 7. RB feeding significantly protected against diarrhea upon virulent HRV challenge and enhanced the protective rate of the vaccine against rotavirus diarrhea. Consistent with protection, RB significantly increased gamma interferon (IFN-γ)-producing CD4(+) and CD8(+) T cell responses in intestinal and systemic lymphoid tissues. Furthermore, RB also increased the number of total IgM- and IgA-secreting cells, total serum IgM, IgG, and IgA titers, and HRV-specific IgA titers in intestinal contents. RB reduced the numbers of intestinal and systemic HRV-specific IgA and IgG antibody-secreting cells and reduced serum HRV-specific IgA and IgG antibody titers before the challenge. These results demonstrate clear beneficial effects of RB in protection against rotavirus diarrhea and stimulation of nonspecific and HRV-specific immune responses, as well as its biased Th1-type adjuvant effect for the vaccine.

Seroprevalence of n-methyl-d-aspartate glutamate receptor (NMDA-R) autoantibodies in aging subjects without neuropsychiatric disorders and in dementia patients

N-methyl-D-aspartate glutamate receptors (NMDA-R) play a key role in learning and memory. Therefore, they may be involved in the pathophysiology of dementia. NMDA-R autoantibodies directed against the NR1a subunit of the NMDA-R, which were first identified as a specific marker for a severe form of encephalitis, cause a decrease in NMDA-Rs, resulting in cognitive impairment and psychosis. We examined the prevalence of NR1a NMDA-R autoantibodies in the serum and cerebrospinal fluid (CSF) of 24 patients with Alzheimer's disease (AD), 20 patients with subcortical ischemic vascular dementia (SIVD), and 274 volunteers without neuropsychiatric disorder. The latter cases showed an association of seropositivity with age. Notably, the overall seroprevalence was not statistically different between dementia patients and matched controls. Further analysis of the patient samples showed that four patients with AD and three patients with SIVD had positive NMDA-R IgM, IgG, and/or IgA autoantibody titers in serum. These patients suffered from psychosis (with the exception of one case). CSF samples were negative for NMDA-R autoantibodies. We conclude that the seroprevalence of NMDA-R-directed autoantibodies is age-related. It has to be clarified by larger studies whether NMDA-R autoantibodies in peripheral blood may predispose patients with AD and SIVD to susceptibility for psychotic episodes if disturbances of blood-brain-barrier integrity occur.

Alleviative Effects of a Kampo (a Japanese Herbal) Medicine "Maoto (Ma-Huang-Tang)" on the Early Phase of Influenza Virus Infection and Its Possible Mode of Action.

A Kampo medicine, maoto, has been prescribed in an early phase of influenza-like illness and used for a treatment of influenza clinically in Japan these days. However, the efficacy of maoto against the virus infection remains to be elucidated. This study was conducted to evaluate the alleviative effects of maoto against early phase of influenza virus infection and its preliminary mode of actions through immune systems. When maoto (0.9 and 1.6 g/kg/day) was orally administered to A/J mice on upper respiratory tract infection of influenza virus A/PR/8/34 from 4 hours to 52 hours postinfection (p.i.) significant antipyretic effect was shown in comparison with water-treated control. Administration of maoto (0.8 and 1.3 g/kg/day) significantly decreased the virus titers in both nasal (NLF) and bronchoalveolar lavage fluids (BALF) at 52 hours p.i., and significantly increased the anti-influenza virus IgM, IgA, and IgG1 antibody titers in NLF, BALF, and serum, respectively. Maoto also increased significantly the influenza virus-bound IgG1 and IgM antibody titers in serum and the virus-bound IgM antibody titer in even the BALF of uninfected A/J mice. These results indicate that maoto exerts antipyretic activity in influenza virus-infected mice and virus reducing effect at an early phase of the infection through probably augmentation of the virus-bound natural antibodies.

Effects of dietary vitamin A content on antibody responses of feedlot calves inoculated intramuscularly with an inactivated bovine coronavirus vaccine

To investigate effects of low dietary vitamin A content on antibody responses in feedlot calves inoculated with an inactivated bovine coronavirus (BCoV) vaccine. 40 feedlot calves. Calves were fed diets containing high (3,300 U/kg) or low (1,100 U/kg) amounts of vitamin A beginning on the day of arrival at a feedlot (day 0) and continuing daily until the end of the study (day 140). Serum retinol concentrations were evaluated in blood samples obtained throughout the study. Calves were inoculated IM with an inactivated BCoV vaccine on days 112 and 126. Blood samples obtained on days 112 and 140 were used for assessment of BCoV-specific serum IgG1, IgG2, IgM, and IgA titers via an ELISA. The low vitamin A diet reduced serum retinol concentrations between days 112 and 140. After the BCoV inoculation and booster injections, predominantly serum IgG1 antibodies were induced in calves fed the high vitamin A diet; however, IgG1 titers were compromised at day 140 in calves fed the low vitamin A diet. Other isotype antibodies specific for BCoV were not affected by the low vitamin A diet. Dietary vitamin A restriction increases marbling in feedlot cattle; however, its effect on antibody responses to vaccines is unknown. A low vitamin A diet compromised the serum IgG1 responses against inactivated BCoV vaccine, which suggested suppressed T-helper 2-associated antibody (IgG1) responses. Thus, low vitamin A diets may compromise the effectiveness of viral vaccines and render calves more susceptible to infectious disease.

Hypolipidemic and antioxidative effects of curcumin on blood parameters, humoral immunity, and jejunum histology in Hy-line hens.

Turmeric (Curcuma Longa Linn) is a medicinal plant that contains curcumin. There is a growing interest in using curcumin powder (CP) as feed additives for antioxidative and antimicrobial properties to improve human health. This study was conducted to determine the appropriate levels of CP on blood parameters, immunity, and histology of jejunum in hens. A total of 200, 58-wk-old Hy-line hens were randomly distributed into 4 treatments (0%, 0.5%, 1.5%, and 2.5% CP or 0, 5, 15, and 25 g/kg feed, respectively) with 5 replicates (10 birds each) for 8 weeks using the completely randomized design. Blood samples were taken from 2 birds per replicate at weeks 61 and 65 to evaluate blood parameters. On weeks 63 and 65, two birds from each replicate received 0.5 ml SRBC (25%) injection in breast muscle and 7 days later, blood samples were collected to evaluate total Ig, IgG, and IgM titers in serum. Two hens were sacrificed at week 65 for the histological study of jejunum. Curcumin reduced triglycerides at 1.5% and 2.5% and cholesterol and LDL at 2.5% (p<0.05). Improvement of total Ig and IgG titers after the 1(st) and 2(nd) injections were observed. Muscle thickness in jejunum increased (p<0.05) at 1.5% curcumin and the length and surface area of villus were enhanced as well. Our results demonstrate that curcumin can be used as an antioxidant at 1.5% and antilipidemic agent at 2.5% in diet.

Identification of antigenic Edwardsiella tarda surface proteins and their role in pathogenesis

Edwardsiella tarda causes an infectious fish disease called edwardsiellosis. Several outer membrane proteins (OMPs) are associated with virulence factors and are attractive as vaccine candidates. In this study, 4 immuno-reactive OMPs of E. tarda were detected using anti-sera from flounder infected with E. tarda. Using matrix-assisted laser desorption/ionization mass spectrometry analyses, 2 of the 4 OMPs were identified as OmpA and murein lipoprotein (Lpp), which are highly conserved surface proteins in gram-negative bacteria. For further characterization of these surface proteins, we generated ompA- and lpp-inactivated mutants by insertion of a kanamycin cassette in the corresponding genes, and named these mutants E. tarda CK99 and CK164, respectively. As expected, immuno-reactive OmpA and Lpp proteins were absent in E. tarda CK99 and CK164, respectively, confirming that OmpA and Lpp are antigenic surface proteins. Interestingly, the LD50 value of E. tarda CK164 in fish (2.0 × 108 colony-forming unit [CFU]/fish) was greater than that of the parental strain (3.0 × 107 CFU/fish). The LD50 of E. tarda CK99 did not differ from that of its parental strain. After administering attenuated E. tarda CK164 to fish, we monitored the E. tarda-specific immune response profile. We observed that the E. tarda-specific serum IgM titer increased in a time-dependent manner, and was much higher than the value observed after the administration of a heat-killed E. tarda control. Moreover, fish vaccinated with E. tarda CK164 were 100% protected when challenged by CK41, a pathogenic strain. Our results suggest that E. tarda CK164 can potentially be used for developing an effective live attenuated vaccine for edwardsiellosis that can be applied in the aquaculture industry.