Differences In Immune Response Research Articles

Differential susceptibility and immune response in chicken and Japanese quail towards Avibacterium paragallinarum

ABSTRACT This study was designed to assess variation in the development of clinical signs, the associated pathological changes and immune activation following experimental Avibacterium paragallinarum (Av. paragallinarum) infection in chicken and Japanese quail. Thirty-three, 4-week-old chicken and Japanese quail were divided into 3 groups, namely (1) naïve control (unhandled) containing 3 birds in each, (2) ‘sham-inoculated (sterile PBS inoculated) group’ with 9 birds in each and (3) ‘infected group (Av. pargallinarum infected) with 19 birds in each. Birds were inoculated with 1.8 × 108 CFU/mL of Av. paragallinarum, while sham inoculated received sterile PBS without Av. paragallinarum. Daily clinical monitoring; blood and tissue samples were collected on 0, 3, 5 and 12 days post-infection. Haemagglutination inhibition (HI) and serum oxidative index were measured to assess immune activation. Nasal discharges constituted prominent clinical signs in chicken. Japanese quail elaborated quicker, slightly higher seroconversion in the HI test. The observed immunoprotection mediated via oxidative changes (systemic malondialdehyde (MDA) level) indicated an unusual way of protection provided by inflammatory leukocytes. Trans-epithelial migration of KUL01+ cells following the putative release of chemo-attractants by turbinates epithelium was evident. Action by reduced glutathione levels (neutralizing MDA) in chicken, not in Japanese quail, suggests species-specific differences of innate immunity against infection.

Differential Immune Response of Lactobacillus plantarum 286 Against Salmonella Typhimurium Infection in Conventional and Germ-Free Mice.

We aimed at evaluating in vivo the probiotic potential of Lactobacillus plantarum 286 against Salmonella enterica serov. Typhimurium. Colonization capacity and antagonistic activity were determined in feces of gnotobiotic mice. Survival to infection, translocation, histopathology, IgA and cytokine levels (IL-10, IL-6, IFN-γ, TNF-α, TGF-β) were determined both in conventional and germ-free mice followed L. plantarum 286 administration and Salmonella infection. L. plantarum 286 colonized the intestine of gnotobiotic mice, where it produced antagonistic substances against S. Typhimurium. In conventional animals, the administration of this strain increased intestinal IgA levels and reduced the inflammatory response and the tissue damage caused by S. Typhimurium. Reduction of tissue damage in the intestine and liver of germ-free animals was also observed, however the immune response elicited was different in either model. L. plantarum 286 showed in vivo probiotic properties in both murine models. Probiotic capacity results may depend on the animal model chosen.

Relationship of Microbial Profile With Airway Immune Response in Eosinophilic or Neutrophilic Inflammation of Asthmatics.

PurposeDifferent characteristics of airway microbiome in asthmatics may lead to differential immune responses, which in turn cause eosinophilic or neutrophilic airway inflammation. However, the relationships among these factors have yet to be fully elucidated.MethodsMicrobes in induced sputum samples were subjected to sequence analysis of 16S rRNA. Airway inflammatory phenotypes were defined as neutrophils (>60%) and eosinophils (>3%), and inflammation endotypes were defined by levels of T helper (Th) 1 (interferon-γ), Th2 (interleukin [IL]-5 and IL-13), Th-17 (IL-17), and innate Th2 (IL-25, IL-33, and thymic stromal lymphopoietin) cytokines, inflammasomes (IL-1β), epithelial activation markers (granulocyte-macrophage colony-stimulating factor and IL-8), and Inflammation (IL-6 and tumor necrosis factor-α) cytokines in sputum supernatants was assessed by enzyme-linked immunosorbent assay.ResultsThe numbers of operational taxonomic units were significantly higher in the mixed (n = 21) and neutrophilic (n = 23) inflammation groups than in the paucigranulocytic inflammation group (n = 19; p < 0.05). At the species level, Granulicatella adiacens, Streptococcus parasanguinis, Streptococcus pneumoniae, Veillonella rogosae, Haemophilus parainfluenzae, and Neisseria perflava levels were significantly higher in the eosinophilic inflammation group (n = 20), whereas JYGU_s levels were significantly higher in the neutrophilic inflammation group compared to the other subtypes (P < 0.05). Additionally, IL-5 and IL-13 concentrations were correlated with the percentage of eosinophils (P < 0.05) and IL-13 levels were positively correlated with the read counts of Porphyromonas pasteri and V. rogosae (P < 0.05). IL-1β concentrations were correlated with the percentage of neutrophils (P < 0.05). had a tendency to be positively correlated with the read count of JYGU_s (P = 0.095), and was negatively correlated with that of S. pneumoniae (P < 0.05).ConclusionsDifference of microbial patterns in airways may induce distinctive endotypes of asthma, which is responsible for the neutrophilic or eosinophilic inflammation in asthma.

BMI, physical activity, and breast cancer subtype in white, black, and Sea Island breast cancer survivors.

Higher BMI, lower rates of physical activity (PA), and hormone receptor-negative breast cancer (BC) subtype are associated with poorer BC treatment outcomes. We evaluated the prevalence of high BMI, low PA level, and BC subtype among survivors with white/European American (EA) and African American (AA) ancestry, as well as a distinct subset of AAs with Sea Island/Gullah ancestry (SI). We used the South Carolina Central Cancer Registry to identify 137 (42 EAs, 66 AAs, and 29 SIs) women diagnosed with BC and who were within 6-21 months of diagnosis. We employed linear and logistic regression to investigate associations between BMI, PA, and age at diagnosis by racial/ethnic group. Most participants (82%) were overweight/obese (P=0.46). BMI was highest in younger AAs (P=0.02). CDC PA guidelines (≥150min/week) were met by only 28% of participants. The frequency of estrogen receptor (ER)-negative BC subtype was lower in EAs and SIs than in AAs (P<0.05). This is the first study to identify differences in obesity and PA rates, and BC subtype in EAs, AAs, and SIs. BMI was higher, PA rates were lower, and frequency of ER-negative BC was higher in AAs as compared to EAs and SIs. This study highlights the need to promote lifestyle interventions among BC survivors, with the goal of reducing the likelihood of a BC recurrence. Integrating dietary and PA interventions into ongoing survivorship care is essential. Future research could evaluate potential differential immune responses linked to the frequency of triple negative BC in AAs.

Association of bovine major histocompatibility complex class I (BoLA-A) alleles with immune response to Brucella abortus strain 19 in calves

In the present study, we analyzed the immune response of calves to Brucella abortus strain 19 vaccine (S19) and its association with MHC class I (BoLA-A) alleles (exons 2–3 and 4–5). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for typing of BoLA-A exon 2–3 with DdeI and TaqI restriction enzymes; and exon 4–5 with HinfI in 45 crossbred calves. The PCR-RFLP analysis revealed five BoLA-A alleles each for exon 2–3 (A10/A19, A19, A18/19, A18 and A31) and exon 4–5 (A, B, C, D and E). Immune response against B. abortus S19 was assessed at the 4th week post vaccination; antibody response by standard tube agglutination test (STAT) and cell-mediated immunity by lymphocyte proliferation and lymphocyte-mediated cytotoxicity assays. Further, the macrophage function in terms of nitrite production was also analyzed. The association analysis of various BoLA-A alleles with the elicitation of immune response revealed that calves with certain defined genotypes induced significantly higher cell-mediated immune response in terms of lymphocyte proliferation with higher stimulation indices (S.I.) of 1.59 (BoLA-A19), 1.49 (A18/19) and 1.52 (HinfI-D); lymphocyte mediated cytotoxicity (55.52 % in A19) and nitrite production (43.40 μM in A31). It is assumed that allelic variants of BoLA-A (exons 2–3 and 4–5) were associated with the differential immune response of calves to B. abortus S19 vaccination. Therefore, further studies on association analysis of MHC class-I genes in large number of cattle may generate more information and might be useful for adapting the alternative approach of exploring genetic resistance in the cattle herd against bovine brucellosis.

Current use and development of fish vaccines in China

In the past decades, the aquaculture industry made great progress in China, which contributes more than 70% yield of the world's farmed fish. Along with the rapid growth of fish production, increased emergence and outbreak of numbers of diseases pose harm to the aquaculture industry and food safety. From the efficient, safe, environmental and ethical aspects, vaccines is definitely the most appropriate and focused method to control different kinds of fish diseases. In China, researchers have done huge works on the fish vaccines, and so far six domestic aquatic vaccine products along with one imported aquatic vaccine have obtained the national veterinary medicine certificate. More critically, some new vaccines have also entered the field experiment stage and showed broad market prospects. In the present review, authors summarize seven aquatic vaccines, including the live vaccine against grass carp hemorrhagic disease, the inactivated vaccine against Aeromonas hydrophila sepsis in fish, the live vaccine against Edwardsiella tarda in turbot, the anti-idiotypic antibody vaccine against Vibrio alginolyticus, V. parahaemolyticus, and E. tarda in Japanese flounder, the cell-cultured inactivated vaccine against grass carp hemorrhagic disease, the inactivated vaccine against fish infectious spleen and kidney necrosis virus (ISKNV), and the genetically engineered live vaccine against V. anguillarum in turbot. Moreover, different delivery routes of fish vaccines are also compared in this review, along with differential fish immune response after vaccination. All these efforts will ultimately benefit the healthy and sustainable development of aquaculture industry in China.

Abstract B045: A novel immune checkpoint regulator in the ovarian cancer microenvironment

Abstract High-grade serous ovarian cancer (HGSC) is the most lethal gynecologic malignancy, accounting for 70–80% of ovarian cancer deaths worldwide. Despite promising results with platinum-based chemotherapy and cytoreductive surgery, more than 75% of women with HGSC will relapse after completion of first-line therapy. The window of opportunity to tailor therapeutic interventions to control progressive disease is limited due to the inherent tumor heterogeneity and genomic instability of HGSC and to how these factors contribute to different immune responses. Recent studies show that biomarkers expressed by specific stromal cell types in the tumor microenvironment may have prognostic value. CD8+ tumor-infiltrating lymphocytes are associated with improved overall survival and have been described in several solid tumors, including HGSC. Nevertheless, the molecular mechanisms underlying the promotion or inhibition of CD8+ lymphocyte infiltration by stromal cells in ovarian cancer are not fully understood. By laser microdissection and transcriptome profiling of tumor tissue samples from HGSC patients, we identified stromal cancer associated fibroblasts (CAF)-specific gene signatures for ovarian cancer that are associated with the survival of patients and with the differential tumor immune response. Among the differentially expressed genes identified, validation study by qPCR, Imaging CyTOF and immunohistochemistry indicated a significant inverse correlation between stromal MFAP5 expression and intratumoral CD8+ T cell density in HGSC tissue samples. MFAP5 is an extracellular matrix glycoprotein and an important component in the assembly of microfibrils. Moreover our recent studies showed that increased stromal MFAP5 expression is associated with poorer survival in HGSOC patients. This led to the hypothesis that MFAP5 could acts as an immune checkpoint mediator by generating an immunosuppressive environment through suppressing CD8+ T cell activation and trafficking in the ovarian tumor tissue. To test this hypothesis, transcriptome profile was performed to identify alternation in immune related genes in ovarian cancer cells treated with rMFAP5. The results showed markedly higher CD47 expression in rMFAP5 treated cells than control cells. CD47 is an integral membrane protein, in both cancer cells and CD8+ T cells. It has been demonstrated to induce apoptosis in CD8+ T cells and trigger inhibitory signals on macrophages to prevent phagocytosis of cancer cells, thus disabling the possibility to activate CD8+ T-cells. We therefore hypothesize that CD47 mediates the effect of MFAP5 on inducing apoptosis in CD8+ T-cells as wells as on preventing macrophage phagocytosis of ovarian cancer cells. Overall, the identification of MFAP5 as a novel stroma-derived immunomodulatory molecule that is associated with patient survival rates and CD8+ T cell densities presents a unique opportunity for the development of new treatment strategies that may improve survival. Citation Format: Sammy Ferri Borgogno, Tsz-Lun Yeung, Cecilia S Leung, Chi Lam Au Yeung, Ying Zhu, Stephen T Wong, Samuel C Mok. A novel immune checkpoint regulator in the ovarian cancer microenvironment [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr B045. doi:10.1158/1535-7163.TARG-19-B045

Differential immune response modulation in early Leishmania amazonensis infection of BALB/c and C57BL/6 macrophages based on transcriptome profiles

The fate of Leishmania infection can be strongly influenced by the host genetic background. In this work, we describe gene expression modulation of the immune system based on dual global transcriptome profiles of bone marrow-derived macrophages (BMDMs) from BALB/c and C57BL/6 mice infected with Leishmania amazonensis. A total of 12,641 host transcripts were identified according to the alignment to the Mus musculus genome. Differentially expressed genes (DEGs) profiling revealed a differential modulation of the basal genetic background between the two hosts independent of L. amazonensis infection. In addition, in response to early L. amazonensis infection, 10 genes were modulated in infected BALB/c vs. non-infected BALB/c macrophages; and 127 genes were modulated in infected C57BL/6 vs. non-infected C57BL/6 macrophages. These modulated genes appeared to be related to the main immune response processes, such as recognition, antigen presentation, costimulation and proliferation. The distinct gene expression was correlated with the susceptibility and resistance to infection of each host. Furthermore, upon comparing the DEGs in BMDMs vs. peritoneal macrophages, we observed no differences in the gene expression patterns of Jun, Fcgr1 and Il1b, suggesting a similar activation trends of transcription factor binding, recognition and phagocytosis, as well as the proinflammatory cytokine production in response to early L. amazonensis infection. Analysis of the DEG profile of the parasite revealed only one DEG among the 8,282 transcripts, indicating that parasite gene expression in early infection does not depend on the host genetic background.

Differential innate immune responses induced by Mycoplasma hyopneumoniae and Mycoplasma hyorhinis in various types of antigen presenting cells

Mycoplasma (M.) hyopneumoniae is the etiological agent of enzootic pneumonia in pigs and is closely related to M. hyorhinis, which can be isolated from the healthy mucosal surfaces of the upper respiratory tract. In rare cases it can also cause arthritis and polyserositis. Since the innate immune system is an important first line of defense and promotes adaptive immune responses, we characterized the innate immune response of various antigen presenting cells (APCs) to M. hyopneumoniae and M. hyorhinis, which differ in their pathogenicity in vivo. Porcine peripheral blood mononuclear cells were infected with different multiplicities of infection (MOI) of live and inactivated porcine mycoplasmas. Both Mycoplasma species induced strong tumour necrosis factor (TNF) responses in monocytes, with a stronger activation by M. hyorhinis. This higher stimulatory activity was also confirmed for CD40 upregulation. Conventional and plasmacytoid dendritic cells (cDC and pDC, respectively) did not or poorly respond to mycoplasmas in terms of TNF expression but more efficiently in terms of CD40 upregulation. Again, these responses were generally stronger with M. hyorhinis than with M. hyopneumoniae. Both Mycoplasma species also activated B cells in terms of CD25 upregulation, proliferation, and IgM secretion. Interestingly, while the induction of CD25 and in particular proliferation was higher with M. hyorhinis, the IgM secretion did not differ between the two species with the exception of the highest dose of M. hyopneumoniae,which appeared to suppress IgM responses. Taken together, our results provide a comparative analysis of innate immune response with different porcine APCs and demonstrate Mycoplasma species-dependent differences, which could relate to their different pathogenicity in vivo.

Whole body vibration elicits differential immune and metabolic responses in obese and normal weight individuals

Traditional aerobic exercise reduces the risk of developing chronic diseases by inducing immune, metabolic, and myokine responses. Following traditional exercise, both the magnitude and time-course of these beneficial responses are different between obese compared to normal weight individuals. Although obesity may affect the ability to engage in traditional exercise, whole body vibration (WBV) has emerged as a more tolerable form of exercise . The impact of WBV on immune, metabolic, and myokine responses as well as differences between normal weight and obese individuals, however, is unknown. PurposeTo determine if WBV elicits differential magnitudes and time-courses of immune, metabolic, and myokine responses between obese and normal weight individuals. Methods21 participants [Obese (OB): n = 11, Age: 33 ± 4 y, percent body fat (%BF): 39.1 ± 2.4% & Normal weight (NW) n = 10, Age: 28 ± 8 y, %BF: 17.4 ± 2.1%] engaged in 10 cycles of WBV exercise [1 cycle = 1 min of vibration followed by 30 s of rest]. Blood samples were collected pre-WBV (PRE), immediately (POST), 3 h (3H), and 24 h (24H) post-WBV and analyzed for leukocytes, insulin, glucose, and myokines (IL-6, decorin, myostatin). ResultsThe peak (3H) percent change in neutrophil counts (OB: 13.9 ± 17.4 vs. NW: 47.2 ± 6.2%Δ; p = 0.007) was different between groups. The percent change in neutrophil percentages was increased in NW (POST: -1.6 ± 2.0 vs. 3H: 13.0 ± 7.2%Δ, p = 0.019) but not OB (p > 0.05). HOMA β-cell function was increased at 24H (PRE: 83.4 ± 5.4 vs. 24H: 131.0 ± 14.1%; p = 0.013) in NW and was not altered in OB (p > 0.05). PRE IL-6 was greater in OB compared to NW (OB: 2.7 ± 0.6 vs. NW: 0.6 ± 0.1 pg/mL; p = 0.011); however, the percent change from PRE to peak (3H) was greater in NW (OB: 148.1 ± 47.9 vs. NW: 1277.9 ± 597.6 %Δ; p = 0.035). Creatine kinase, decorin, and myostatin were not significantly altered in either group (p > 0.05). ConclusionTaken together, these data suggest that acute whole body vibration elicits favorable immune, metabolic, and myokine responses and that these responses differ between obese and normal weight individuals.

Group B Streptococcus serotypes Ia and V induce differential vaginal immune responses that may contribute to long term colonization of the female reproductive tract.

Group B Streptococcus (GBS) is a common colonizer of the female genital tract at the time of pregnancy and has been associated with severe neonatal infections. Despite trials for GBS vaccines already being underway, the factors influencing vaginal GBS colonization and clearance are currently poorly understood. Within this study, we investigated the host immune responses to GBS infections in mice that affect GBS vaginal colonization and clearance. Cervicovaginal swabs were used to measure vaginal GBS persistence, and vaginal cytokine responses were measured using the BioPlex® system. Lymphocytes isolated from spleens were stimulated with UV-killed GBS to examine systemic cellular responses. Additional in vitro cellular experiments using human vaginal epithelial cells were also performed, examining the effect pregnancy level hormones had on GBS adhesion, invasion, and cytokine responses. We observed significant differences in the ability of GBS serotype V infections to persist, compared with GBS serotype Ia vaginal infections. Vaginal cytokine response examination identified temporal changes in cytokine production (IL10, IFNγ, IL6, IL1β, and TNFα) in relation to GBS serotype and clearance or colonization. Lymphocyte proliferation assays also revealed robust cellular immune responses to GBS vaginal infections irrespective of clearance or colonization. In vitro human cellular analyses also identified that vaginal epithelial cell line cytokine production was suppressed in the presence of hormones despite no alteration in adhesion/invasion. Here, we establish previously unknown, serotype specific, temporal immune responses which may be associated with vaginal GBS colonization or clearance in the female genital tract.

Asian and African lineage Zika viruses show differential replication and innate immune responses in human dendritic cells and macrophages

Zika virus (ZIKV) infections in humans are considered to be mild or subclinical. However, during the recent epidemics in the Pacific Islands and the Americas, the infection was associated with Quillain-Barré syndrome and congenital infections with fetal brain abnormalities, including microcephaly. Thus, more detailed understanding of ZIKV-host cell interactions and regulation of innate immune responses by strains of differential evolutionary origin is required. Here, we characterized the infection and immune responses triggered by two epidemic Asian/American lineage viruses, including an isolate from fetal brains, and a historical, low passage 1947 African lineage virus in human monocyte-derived dendritic cells (DCs) and macrophages. The epidemic Asian/American ZIKV replicated well and induced relatively good antiviral responses in human DCs whereas the African strain replicated less efficiently and induced weaker immune responses. In macrophages both the African and Asian strains showed limited replication and relatively weak cytokine gene expression. Interestingly, in macrophages we observed host protein degradation, especially IRF3 and STAT2, at early phases of infection with both lineage viruses, suggesting an early proteasomal activation in phagocytic cells. Our data indicates that ZIKV evolution has led to significant phenotypic differences in the replication characteristics leading to differential regulation of host innate immune responses.

2782. Host Immune Response to Enterovirus and Parechovirus Systemic Infections in Children

BackgroundEnterovirus (EV) and human Parechovirus (PeV) cause a range of illness including asymptomatic to systemic infections. The host immune response in children, especially the one induced by PeV, is largely unknown. The aim of this study was to determine the immune response induced by EV and PeV in cerebrospinal fluid (CSF) and plasma obtained from children with systemic infection.MethodsLeft-over CSF and paired blood samples collected from children with laboratory confirmed EV and PeV central nervous system-infection were enrolled in this study. EV/PeV-negative CSF and paired plasma from children was used as controls. Level of cytokines and chemokines were measured using a customized 21-plex ELISA panel that included 16 cytokines and 5 chemokines (Millipore, CA). Additionally, clinical characteristics of all the patients were collected to determine the potential association between the immune response and pathogenicity.ResultsTotal of 74 samples were enrolled and divided into 3 groups, EV (n = 27), PeV (n = 23) and control group (n = 24). Median age of all the three groups was 2 weeks (IQR 2–4 weeks).The key analytes which had a significant difference between each groups are show in the Table. In general, EV induced more robust cytokine secretion than PeV and control group. Anti-viral response such as IFN-g was remarkably absent in both CSF and plasma in PeV group compared with EV group (P < 0.05). Only IL-8 was significantly higher (P < 0.05) in EV CSF group compared with any other groups or sample types. Level of all the chemokines measured were much higher in all the three groups but significant difference was found between PeV CSF and plasma for IP-10 and MCP-1 chemokines (P < 0.05).ConclusionIn this study, we demonstrate that EV and PeV induces distinct immune response in children with systemic infections. While EV induces more robust inflammation, PeV-induced inflammation appears to be either weak or absent in CSF, but robust in plasma. The suppressed pro-inflammatory response might facilitate PeV growth and proliferation in CSF and might play a role in disease severity. Further studies are needed to fully understand the differential immune response induced by these two viruses. Disclosures All authors: No reported disclosures.

Differential Susceptibility and Innate Immune Response of Aedes aegypti and Aedes albopictus to the Haitian Strain of the Mayaro Virus.

Mayaro (MAYV) is an emerging arthropod-borne virus belonging to the Alphavirus genus of the Togaviridae family. Although forest-dwelling Haemagogus mosquitoes have been considered as its main vector, the virus has also been detected in circulating Aedes ssp mosquitoes. Here we assess the susceptibility of Aedes aegypti and Aedes albopictus to infection with MAYV and their innate immune response at an early stage of infection. Aedes albopictus was more susceptible to infection with MAYV than Ae. aegypti. Analysis of transcript levels of twenty immunity-related genes by real-time PCR in the midgut of both mosquitoes infected with MAYV revealed increased expression of several immune genes, including CLIP-domain serine proteases, the anti-microbial peptides defensin A, E, cecropin E, and the virus inducible gene. The regulation of certain genes appeared to be Aedes species-dependent. Infection of Ae. aegypti with MAYV resulted in increased levels of myeloid differentiation2-related lipid recognition protein (ML26A) transcripts, as compared to Ae. albopictus. Increased expression levels of thio-ester-containing protein 22 (TEP22) and Niemann–Pick type C1 (NPC1) gene transcripts were observed in infected Ae. albopictus, but not Ae. aegypti. The differences in these gene expression levels during MAYV infection could explain the variation in susceptibility observed in both mosquito species.

Differential Immune Responses to Hemorrhagic Fever-Causing Arenaviruses.

The family Arenaviridae contains several pathogens of major clinical importance. The Old World (OW) arenavirus Lassa virus is endemic in West Africa and is estimated to cause up to 300,000 infections each year. The New World (NW) arenaviruses Junín and Machupo periodically cause hemorrhagic fever outbreaks in South America. While these arenaviruses are highly pathogenic in humans, recent evidence indicates that pathogenic OW and NW arenaviruses interact with the host immune system differently, which may have differential impacts on viral pathogenesis. Severe Lassa fever cases are characterized by profound immunosuppression. In contrast, pathogenic NW arenavirus infections are accompanied by elevated levels of Type I interferon and pro-inflammatory cytokines. This review aims to summarize recent findings about interactions of these pathogenic arenaviruses with the innate immune machinery and the subsequent effects on adaptive immunity, which may inform the development of vaccines and therapeutics against arenavirus infections.

Disparate Entry of Adenoviruses Dictates Differential Innate Immune Responses on the Ocular Surface.

Human adenovirus infection of the ocular surface is associated with severe keratoconjunctivitis and the formation of subepithelial corneal infiltrates, which may persist and impair vision for months to years following infection. Long term pathology persists well beyond the resolution of viral replication, indicating that the prolonged immune response is not virus-mediated. However, it is not clear how these responses are sustained or even initiated following infection. This review discusses recent work from our laboratory and others which demonstrates different entry pathways specific to both adenovirus and cell type. These findings suggest that adenoviruses may stimulate specific pattern recognition receptors in an entry/trafficking-dependent manner, leading to distinct immune responses dependent on the virus/cell type combination. Additional work is needed to understand the specific connections between adenoviral entry and the stimulation of innate immune responses by the various cell types present on the ocular surface.

Differential survival of 3rd stage larvae of Contracaecum rudolphii type B infecting common bream (Abramis brama) and common carp (Cyprinus carpio)

The main fish host reaction to an infection with third stage anisakid nematode larvae is a response in which host immune cells (macrophages, granulocytes, lymphocytes) in affected internal organs initially are attracted to the parasite whereafter fibroblasts may enclose the parasite forming granuloma. Generally, the reaction is non-lethal to the parasite which may survive for years in the fish host retaining infectivity to the final host. This may also apply for the anisakid nematode Contracaecum rudolphii (having the adult stage in cormorants, using copepods as first intermediate/paratenic host and zooplankton feeding fish as paratenic hosts). The present study has shown that most Contracaecum rudolphii larvae survive in bream (Abramis brama) (from Lake Balaton, Hungary) whereas the majority of the nematode larvae die in Cyprinus carpio (from Lake Hévíz, directly connected to Lake Balaton). Both cyprinid host species interacted with the nematode larvae through establishing a marked cellular encapsulation around them but with different effects. The differential survival in common carp and bream may theoretically be explained by ecological factors, such as the environmental temperature which either directly or indirectly affect the development of nematode larvae, and/or intrinsic host factors, such as differential immune responses and host genetics.

Impact of aging on the immune response to traumatic brain injury (AIm:TBI) study protocol

BackgroundTraumatic brain injury (TBI) in older adults leads to considerable morbidity and mortality. Outcomes among older adults with TBI are disparately worse than in younger adults. Differences in immunological response...

Differential Tick Salivary Protein Profiles and Human Immune Responses to Lone Star Ticks (Amblyomma americanum) From the Wild vs. a Laboratory Colony.

Ticks are a growing concern to human and animal health worldwide and they are leading vectors of arthropod-borne pathogens in the United States. Ticks are pool blood feeders that can attach to the host skin for days to weeks using their saliva to counteract the host defenses. Tick saliva, as in other hematophagous arthropods, contains pharmacological and immunological active compounds, which modulate local and systemic immune responses and induce antibody production. In the present study, we explore differences in the salivary gland extract (SGE) protein content of Amblyomma americanum ticks raised in a laboratory colony (CT) vs. those collected in the field (FT). First, we measured the IgG antibody levels against SGE in healthy volunteers residing in Kansas. ELISA test showed higher IgG antibody levels when using the SGE from CT as antigen. Interestingly, antibody levels against both, CT-SGE and FT-SGE, were high in the warm months (May–June) and decreased in the cold months (September–November). Immunoblot testing revealed a set of different immunogenic bands for each group of ticks and mass spectrometry data revealed differences in at 19 proteins specifically identified in the CT-SGE group and 20 from the FT-SGE group. Our results suggest that differences in the salivary proteins between CT-SGE and FT-SGE may explain the differential immune responses observed in this study.

Alterations in Blood Monocyte Functions in Parkinson's Disease.

PD is a multisystem disease where both central and peripheral nervous systems are affected. This systemic involvement also includes the immune response in PD, which implicates not only microglia in the brain, but also peripheral immune cells, such as monocytes; however, this aspect has been understudied. The purpose of this study was to investigate the PD-related changes in peripheral immune cells, their responsiveness to stimulation, and their ability to release immunomodulatory molecules that might have consequences for the disease progression. Using flow cytometry, we investigated the monocytic population in peripheral blood mononuclear cells from PD patients and healthy individuals. We also evaluated the in vitro response to inflammogen lipopolysaccharides and to fibrillar α-synuclein by measuring the expression of CD14, CD163, and HLA-DR and by analysis of soluble immune-related molecules in the supernatant. Peripheral blood immune cells from PD patients had lower survival in culture, but showed a higher monocytic proliferative ability than control cells, which was correlated with shorter disease duration and late disease onset. In addition, PD patients' cells were less responsive to stimulation, as shown by the lack of changes in CD163 and CD14 expression, and by the absence of significant upregulation of anti-inflammatory cytokines in culture. Moreover, PD peripheral immune cells shed lower in vitro levels of soluble CD163, which suggests a less responsive monocytic population and/or an activation status different from control cells. Interestingly, some of the results were sex associated, supporting a differential immune response in females versus males. Our data suggest that PD involves monocytic changes in blood. These cells show reduced viability and are unresponsive to specific stimuli, which might have a relevant consequence for disease progression. © 2019 International Parkinson and Movement Disorder Society.