Mastomys natalensis Has a Cellular Immune Response Profile Distinct from Laboratory Mice

The multimammate mouse (Mastomys natalensis; M. natalensis) has been identified as a major reservoir for multiple human pathogens including Lassa virus (LASV), Leishmania spp., Yersinia spp., and Borrelia spp. Although M. natalensis are related to well-characterized mouse and rat species commonly used in laboratory models, there is an absence of established assays and reagents to study the host immune responses of M. natalensis. As a result, there are major limitations to our understanding of immunopathology and mechanisms of immunological pathogen control in this increasingly important rodent species. In the current study, a large panel of commercially available rodent reagents were screened to identify their cross-reactivity with M. natalensis. Using these reagents, ex vivo assays were established and optimized to evaluate lymphocyte proliferation and cytokine production by M. natalensis lymphocytes. In contrast to C57BL/6J mice, lymphocytes from M. natalensis were relatively non-responsive to common stimuli such as phytohaemagglutinin P and lipopolysaccharide. However, they readily responded to concanavalin A stimulation as indicated by proliferation and cytokine production. In summary, we describe lymphoproliferative and cytokine assays demonstrating that the cellular immune responses in M. natalensis to commonly used mitogens differ from a laboratory-bred mouse strain.

Download Full-text

Tandem antioxidant enzymes confer synergistic protective responses in experimental filariasis

Journal of Helminthology ◽

10.1017/s0022149x13000333 ◽

2013 ◽

Vol 88 (4) ◽

pp. 402-410 ◽

Cited By ~ 6

Author(s):

P.R. Prince ◽

J. Madhumathi ◽

G. Anugraha ◽

P.J. Jeyaprita ◽

M.V.R. Reddy ◽

...

Keyword(s):

Immune Responses ◽

Redox Regulation ◽

Protective Efficacy ◽

Wuchereria Bancrofti ◽

Parasite Clearance ◽

Cross Reactivity ◽

Host Responses ◽

Enzyme Linked Immunosorbent Assay ◽

Helminth Parasites ◽

Cellular Immune

AbstractHelminth parasites use antioxidant defence strategies for survival during oxidative stress due to free radicals in the host. Accordingly, tissue-dwelling filarial parasites counteract host responses by releasing a number of antioxidants. Targeting these redox regulation proteins together, would facilitate effective parasite clearance. Here, we report the combined effect of protective immune responses trigged by recombinant Wuchereria bancrofti thioredoxin (WbTRX) and thioredoxin peroxidase (WbTPX) in an experimental filarial model. The expression of WbTRX and WbTPX in different stages of the parasite and their cross-reactivity were analysed by enzyme-linked immunosorbent assay (ELISA). The immunogenicity of recombinant proteins and their protective efficacy were studied in animal models when immunized in single or cocktail mode. The antigens showed cross-reactive epitopes and induced high humoral and cellular immune responses in mice. Further, parasite challenge against Brugia malayi L3 larvae in Mastomyscoucha conferred significant protection of 57% and 62% against WbTRX and WbTPX respectively. The efficacy of L3 clearance was significantly higher (71%) (P < 0.001) when the antigens were immunized together, showing a synergistic effect in multiple-mode vaccination. Hence, the study suggests WbTRX and WbTPX to be attractive vaccine candidates when immunized together and provides a tandem block for parasite elimination in the control of lymphatic filariasis.

Download Full-text

Modulation of Host-Immune Responses by Ticks (Acari: Ixodidae): Effect of Salivary Gland Extracts on Host Macrophages and Lymphocyte Cytokine Production

Journal of Medical Entomology ◽

10.1093/jmedent/29.5.818 ◽

1992 ◽

Vol 29 (5) ◽

pp. 818-826 ◽

Cited By ~ 113

Author(s):

Rangappa N. Ramachandra ◽

Stephen K. Wikel

Keyword(s):

Salivary Gland ◽

Immune Responses ◽

Cytokine Production ◽

Host Immune Responses

Download Full-text

Host immune responses in ex vivo approaches to cutaneous gene therapy targeted to keratinocytes

Experimental Dermatology ◽

10.1111/j.1600-0625.2005.00351.x ◽

2005 ◽

Vol 14 (10) ◽

pp. 727-735 ◽

Cited By ~ 19

Author(s):

Z. Lu ◽

S. Ghazizadeh

Keyword(s):

Gene Therapy ◽

Immune Responses ◽

Ex Vivo ◽

Host Immune Responses

Download Full-text

Exploratory Study on Plasma Immunomodulator and Antibody Profiles in Tuberculosis Patients

Clinical and Vaccine Immunology ◽

10.1128/cvi.00213-13 ◽

2013 ◽

Vol 20 (8) ◽

pp. 1283-1290 ◽

Cited By ~ 13

Author(s):

Resmi Ravindran ◽

Viswanathan V. Krishnan ◽

Azra Khanum ◽

Paul A. Luciw ◽

Imran H. Khan

Keyword(s):

Immune Responses ◽

Ex Vivo ◽

Peripheral Circulation ◽

Computer Assisted ◽

Content Type ◽

Tuberculosis Patients ◽

Active Pulmonary Tuberculosis ◽

Host Immune Responses ◽

Data Points ◽

Apparently Healthy

ABSTRACTHost immune responses toMycobacterium tuberculosisare generally able to contain infection and maintain a delicate balance between protection and immunopathology. A shift in this balance appears to underlie active disease observed in about 10% of infected individuals. Effects of local inflammation, combined with anti-M. tuberculosissystemic immune responses, are directly detectable in peripheral circulation, withoutex vivostimulation of blood cells or biopsy of the affected organs. We studied plasma immunomodulator and antibody biomarkers in patients with active pulmonary tuberculosis (TB) by a combination of multiplex microbead immunoassays and computational tools for data analysis. Plasma profiles of 10 immunomodulators and antibodies against eightM. tuberculosisantigens (previously reported by us) were examined in active pulmonary TB patients in a country where TB is endemic, Pakistan. Multiplex analyses were performed on samples from apparently healthy individuals without active TB from the same community as the TB patients to establish the assay baselines for all analytes. Over 3,000 data points were collected from patients (n= 135) and controls (n= 37). The data were analyzed by multivariate and computer-assisted cluster analyses to reveal patterns of plasma immunomodulators and antibodies. This study shows plasma profiles that in most patients represented either strong antibody or strong immunomodulator biomarkers. Profiling of a combination of both immunomodulators and antibodies described here may be valuable for the analysis of host immune responses in active TB in countries where the disease is endemic.

Download Full-text

Inhibition of Innate Immune Responses Is Key to Pathogenesis by Arenaviruses

Journal of Virology ◽

10.1128/jvi.03049-15 ◽

2016 ◽

Vol 90 (8) ◽

pp. 3810-3818 ◽

Cited By ~ 24

Author(s):

Bjoern Meyer ◽

Hinh Ly

Keyword(s):

Immune Responses ◽

Immune Evasion ◽

Molecular Mechanisms ◽

Multiorgan Failure ◽

Hemorrhagic Fever ◽

Innate Immune ◽

Lassa Virus ◽

Immune Recognition ◽

African Countries ◽

Host Immune Responses

Mammalian arenaviruses are zoonotic viruses that cause asymptomatic, persistent infections in their rodent hosts but can lead to severe and lethal hemorrhagic fever with bleeding and multiorgan failure in human patients. Lassa virus (LASV), for example, is endemic in several West African countries, where it is responsible for an estimated 500,000 infections and 5,000 deaths annually. There are currently no FDA-licensed therapeutics or vaccines available to combat arenavirus infection. A hallmark of arenavirus infection (e.g., LASV) is general immunosuppression that contributes to high viremia. Here, we discuss the early host immune responses to arenavirus infection and the recently discovered molecular mechanisms that enable pathogenic viruses to suppress host immune recognition and to contribute to the high degree of virulence. We also directly compare the innate immune evasion mechanisms between arenaviruses and other hemorrhagic fever-causing viruses, such as Ebola, Marburg, Dengue, and hantaviruses. A better understanding of the immunosuppression and immune evasion strategies of these deadly viruses may guide the development of novel preventative and therapeutic options.

Download Full-text

Cross-Protection against Challenge with Puumala Virus after Immunization with Nucleocapsid Proteins from Different Hantaviruses

Journal of Virology ◽

10.1128/jvi.76.13.6669-6677.2002 ◽

2002 ◽

Vol 76 (13) ◽

pp. 6669-6677 ◽

Cited By ~ 48

Author(s):

Cristina de Carvalho Nicacio ◽

Marcelo Gonzalez Della Valle ◽

Paula Padula ◽

Ewa Björling ◽

Alexander Plyusnin ◽

...

Keyword(s):

T Lymphocytes ◽

Immune Responses ◽

Hemorrhagic Fever ◽

Cross Reactivity ◽

Cross Protection ◽

Laboratory Animals ◽

Homologous Protein ◽

Humoral Responses ◽

Cellular Immune

ABSTRACT Hantaviruses are rodent-borne agents that cause hemorrhagic fever with renal syndrome or hantavirus pulmonary syndrome in humans. The nucleocapsid protein (N) is relatively conserved among hantaviruses and highly immunogenic in both laboratory animals and humans, and it has been shown to induce efficient protective immunity in animal models. To investigate the ability of recombinant N (rN) from different hantaviruses to elicit cross-protection, we immunized bank voles with rN from Puumala (PUUV), Topografov (TOPV), Andes (ANDV), and Dobrava (DOBV) viruses and subsequently challenged them with PUUV. All animals immunized with PUUV and TOPV rN were completely protected. In the group immunized with DOBV rN, 7 of 10 animals were protected, while only 3 of 8 animals were protected in the group immunized with ANDV rN, which is more closely related to PUUV rN than DOBV rN. Humoral and cellular immune responses after rN immunization were also investigated. The highest cross-reactive humoral responses against PUUV antigen were detected in sera from ANDV rN-immunized animals, followed by those from TOPV rN-immunized animals, and only very low antibody cross-reactivity was observed in sera from DOBV rN-immunized animals. In proliferation assays, T lymphocytes from animals immunized with all heterologous rNs were as efficiently recalled in vitro by PUUV rN as were T lymphocytes from animals immunized with homologous protein. In summary, this study has shown that hantavirus N can elicit cross-protective immune responses against PUUV, and the results suggest a more important role for the cellular arm of the immune response than for the humoral arm in cross-protection elicited by rN.

Download Full-text

Severe Symptomatic Primary Human Cytomegalovirus Infection despite Effective Innate and Adaptive Immune Responses

Journal of Virology ◽

10.1128/jvi.02245-16 ◽

2016 ◽

Vol 91 (5) ◽

Cited By ~ 6

Author(s):

Raphaëlle Riou ◽

Céline Bressollette-Bodin ◽

David Boutoille ◽

Katia Gagne ◽

Audrey Rodallec ◽

...

Keyword(s):

T Cells ◽

Immune Responses ◽

Human Cytomegalovirus ◽

Hcmv Infection ◽

Cytokine Production ◽

Lymphocyte Activation ◽

Adaptive Immune Responses ◽

Host Immune Responses ◽

Adaptive Immune ◽

Cell Compartments

ABSTRACT Primary human cytomegalovirus (HCMV) infection usually goes unnoticed, causing mild or no symptoms in immunocompetent individuals. However, some rare severe clinical cases have been reported without investigation of host immune responses or viral virulence. In the present study, we investigate for the first time phenotypic and functional features, together with gene expression profiles in immunocompetent adults experiencing a severe primary HCMV infection. Twenty primary HCMV-infected patients (PHIP) were enrolled, as well as 26 HCMV-seronegative and 39 HCMV-seropositive healthy controls. PHIP had extensive lymphocytosis marked by massive expansion of natural killer (NK) and T cell compartments. Interestingly, PHIP mounted efficient innate and adaptive immune responses with a deep HCMV imprint, revealed mainly by the expansion of NKG2C+ NK cells, CD16+ Vδ2(−) γδ T cells, and conventional HCMV-specific CD8+ T cells. The main effector lymphocytes were activated and displayed an early immune phenotype that developed toward a more mature differentiated status. We suggest that both massive lymphocytosis and excessive lymphocyte activation could contribute to massive cytokine production, known to mediate tissue damage observed in PHIP. Taken together, these findings bring new insights into the comprehensive understanding of immune mechanisms involved during primary HCMV infection in immunocompetent individuals. IMPORTANCE HCMV-specific immune responses have been extensively documented in immunocompromised patients and during in utero acquisition. While it usually goes unnoticed, some rare severe clinical cases of primary HCMV infection have been reported in immunocompetent patients. However, host immune responses or HCMV virulence in these patients has not so far been investigated. In the present study, we show massive expansion of NK and T cell compartments during the symptomatic stage of acute HCMV infection. The patients mounted efficient innate and adaptive immune responses with a deep HCMV imprint. The massive lymphocytosis could be the result of nonadapted or uncontrolled immune responses limiting the effectiveness of the specific responses mounted. Both massive lymphocytosis and excessive lymphocyte activation could contribute to massive cytokine production, known to mediate tissue damage. Furthermore, we cannot exclude a delayed immune response caused by immune escape established by HCMV strains.

Download Full-text

A model symbiosis reveals a role for sheathed-flagellum rotation in the release of immunogenic lipopolysaccharide

eLife ◽

10.7554/elife.01579 ◽

2014 ◽

Vol 3 ◽

Cited By ~ 26

Author(s):

Caitlin A Brennan ◽

Jason R Hunt ◽

Natacha Kremer ◽

Benjamin C Krasity ◽

Michael A Apicella ◽

...

Keyword(s):

Immune Responses ◽

Unknown Function ◽

Vibrio Fischeri ◽

Host Responses ◽

Tissue Tropism ◽

Human Pathogens ◽

Bacterial Flagella ◽

Host Immune Responses ◽

Microbe Interactions ◽

Host Microbe Interactions

Bacterial flagella mediate host–microbe interactions through tissue tropism during colonization, as well as by activating immune responses. The flagellar shaft of some bacteria, including several human pathogens, is encased in a membranous sheath of unknown function. While it has been hypothesized that the sheath may allow these bacteria to evade host responses to the immunogenic flagellin subunit, this unusual structural feature has remained an enigma. Here we demonstrate that the rotation of the sheathed flagellum in both the mutualist Vibrio fischeri and the pathogen Vibrio cholerae promotes release of a potent bacteria-derived immunogen, lipopolysaccharide, found in the flagellar sheath. We further present a new role for the flagellar sheath in triggering, rather than circumventing, host immune responses in the model squid-vibrio symbiosis. Such an observation not only has implications for the study of bacterial pathogens with sheathed flagella, but also raises important biophysical questions of sheathed-flagellum function.

Download Full-text

GH18 family glycoside hydrolase Chitinase A of Salmonella facilitates bacterial invasion and survival by modulating host immune responses

10.1101/2021.07.13.452150 ◽

2021 ◽

Author(s):

Kasturi Chandra ◽

Dipshikha Chakravortty

Keyword(s):

Immune Responses ◽

Defense Mechanisms ◽

Salmonella Typhi ◽

Bacterial Invasion ◽

Human Pathogens ◽

C Elegans ◽

Host Immune Responses ◽

Gut Colonization ◽

Chitinase A

Salmonella is a facultative intracellular pathogen that has co-evolved with its host and has also developed various strategies to evade the host immune responses. Salmonella recruits an array of virulence factors to escape from host defense mechanisms. Previously chitinase A (chiA) was found to be upregulated in intracellular Salmonella. Although studies show that chitinases and chitin binding proteins (CBP) of many human pathogens have a profound role in various aspects of pathogenesis, like adhesion, virulence and immune evasion, the role of chitinase in strict intravacuolar pathogen Salmonella has not yet been elucidated. In this study, we deciphered the role of chitinase of Salmonella in the pathogenesis of the serovars, Typhimurium and Typhi. Our data propose that ChiA mediated modification of the glycosylation on the epithelial cell surface facilitates the invasion of the pathogen into the epithelial cells. Further we found that ChiA aids in reactive nitrogen species (RNS) and reactive oxygen species (ROS) production in phagocytes, leading to MHCII downregulation followed by suppression of antigen presentation and antibacterial responses. In continuation of the study in animal model C. elegans, Salmonella Typhi ChiA was found to facilitate attachment to the intestinal epithelium, gut colonization and persistence by downregulating antimicrobial peptides.

Download Full-text