Mathematical modeling and analysis of innate and humoral immune responses to dengue infections

2019 ◽  
Vol 12 (07) ◽  
pp. 1950077 ◽  
Author(s):  
Sulanie Perera ◽  
S. S. N. Perera

Dengue is an acute arthropode-borne virus, belonging to the family Flaviviridae. Currently, there are no vaccines or treatments available against dengue. Thus it is important to understand the dynamics of dengue in order to control the infection. In this paper, we study the long-term dynamics of the model that is presented in [S. D. Perera and S. S. N. Perera, Simulation model for dynamics of dengue with innate and humoral immune responses, Comput. Math. Methods Med. 2018 (2018) 8798057, 18 pp. https://doi.org/10.1155/2018/8798057 ] which describes the interaction of virus with infected and uninfected cells in the presence of innate and humoral immune responses. It was found the model has three equilibria, namely: infection free equilibrium, no immune equilibrium and endemic equilibrium, then analyzed its stability analytically. The analytical findings of each model have been exemplified by numerical simulations. Given the fact that intensity of dengue virus replication at early times of infection could determine clinical outcomes, it is important to understand the impact of innate immunity, which is believed to be the first line of defense against an invading pathogen. For this we carry out a simulation case study to investigate the importance of innate immune response on dengue virus dynamics. A comparison was done assuming that innate immunity was active; innate immunity was in quasi-steady state and innate immunity was inactive during the virus replication process. By a further analysis of the qualitative behavior of the quasi-steady state, it was observed that innate immune response plays a pivotal role in dengue virus dynamics. It can change the dynamical behavior of the system and is essential for the virus clearance.

2018 ◽  
Vol 2018 ◽  
pp. 1-18 ◽  
Author(s):  
S. D. Perera ◽  
S. S. N. Perera

Dengue virus is a mosquito borne Flavivirus and the most prevalent arbovirus in tropical and subtropical regions around the world. The incidence of dengue has increased drastically over the last few years at an alarming rate. The clinical manifestation of dengue ranges from asymptomatic infection to severe dengue. Even though the viral kinetics of dengue infection is lacking, innate immune response and humoral immune response are thought to play a major role in controlling the virus count. Here, we developed a computer simulation mathematical model including both innate and adaptive immune responses to study the within-host dynamics of dengue virus infection. A sensitivity analysis was carried out to identify key parameters that would contribute towards severe dengue. A detailed stability analysis was carried out to identify relevant range of parameters that contributes to different outcomes of the infection. This study provides a qualitative understanding of the biological factors that can explain the viral kinetics during a dengue infection.


Blood ◽  
2009 ◽  
Vol 113 (11) ◽  
pp. 2461-2469 ◽  
Author(s):  
Henrik E. Mei ◽  
Taketoshi Yoshida ◽  
Wondossen Sime ◽  
Falk Hiepe ◽  
Kathi Thiele ◽  
...  

AbstractProviding humoral immunity, antibody-secreting plasma cells and their immediate precursors, the plasmablasts, are generated in systemic and mucosal immune reactions. Despite their key role in maintaining immunity and immunopathology, little is known about their homeostasis. Here we show that plasmablasts and plasma cells are always detectable in human blood at low frequency in any unimmunized donor. In this steady state, 80% of plasmablasts and plasma cells express immunoglobulin A (IgA). Expression of a functional mucosal chemokine receptor, C-C motif receptor 10 (CCR10) and the adhesion molecule β7 integrin suggests that these cells come from mucosal immune reactions and can return to mucosal tissue. These blood-borne, CCR10+ plasmablasts also are attracted by CXCL12. Approximately 40% of plasma cells in human bone marrow are IgA+, nonmigratory, and express β7 integrin and CCR10, suggesting a substantial contribution of mucosal plasma cells to bone marrow resident, long-lived plasma cells. Six to 8 days after parenteral tetanus/diphtheria vaccination, intracellular IgG+ cells appear in blood, both CD62L+, β7 integrin−, dividing, vaccine-specific, migratory plasmablasts and nondividing, nonmigratory, CD62L− plasma cells of different specificities. Systemic vaccination does not impact on peripheral IgA+ plasmablast numbers, indicating that mucosal and systemic humoral immune responses are regulated independent of each other.


1999 ◽  
Vol 41 (2) ◽  
pp. 107-114 ◽  
Author(s):  
J. MEGID ◽  
M.T.S. PERAÇOLI ◽  
P.R. CURI ◽  
C.R. ZANETTI ◽  
W.H. CABRERA ◽  
...  

The cellular and humoral immune responses of mice inoculated with rabies virus and treated with the Bacillus of Calmette-Guérin, Avridine and Propionibacterium acnes were evaluated in this paper. There was a higher percentage of surviving mice in groups submitted to P. acnes treatment. Lower levels of interferon-<FONT FACE="Symbol">g</font> (IFN-<FONT FACE="Symbol">g</font>) were found in infected mice. The intra-pad inoculation test (IPI) was not effective to detect cellular immune response, contrary to the results found in MIF reaction. The survival of mice did not present correlation with the levels of antirabies serum neutralizing (SN) antibodies titers, IFN-<FONT FACE="Symbol">g</font> concentration and MIF response.


PLoS ONE ◽  
2014 ◽  
Vol 9 (6) ◽  
pp. e98319 ◽  
Author(s):  
Yoshihisa Mizukami ◽  
Tomoyuki Abe ◽  
Hiroaki Shibata ◽  
Yukitoshi Makimura ◽  
Shuh-hei Fujishiro ◽  
...  

2014 ◽  
Vol 11 (6) ◽  
pp. 70-75
Author(s):  
A V Sobolev ◽  
O V Aak

Recovering from bacterial infections in the first years of life reduces further risk of allergic diseases. Effects of bacterial immunomodulator Broncho Vaxom on immune system to certain extent repeats the immune response that occurs during penetration of the pathogen in the body. Bacterial antigens orchestrate cellular and humoral immune responses, stimulate innate immunity, normalize cytokine balance, and are promising in the treatment of respiratory allergic diseases.


2005 ◽  
Vol 79 (22) ◽  
pp. 13915-13923 ◽  
Author(s):  
Wing-pui Kong ◽  
Ling Xu ◽  
Konrad Stadler ◽  
Jeffrey B. Ulmer ◽  
Sergio Abrignani ◽  
...  

ABSTRACT Although the initial isolates of the severe acute respiratory syndrome (SARS) coronavirus (CoV) are sensitive to neutralization by antibodies through their spike (S) glycoprotein, variants of S have since been identified that are resistant to such inhibition. Optimal vaccine strategies would therefore make use of additional determinants of immune recognition, either through cellular or expanded, cross-reactive humoral immunity. Here, the cellular and humoral immune responses elicited by different combinations of gene-based and inactivated viral particles with various adjuvants have been assessed. The T-cell response was altered by different prime-boost immunizations, with the optimal CD8 immunity induced by DNA priming and replication-defective adenoviral vector boosting. The humoral immune response was enhanced most effectively through the use of inactivated virus with adjuvants, either MF59 or alum, and was associated with stimulation of the CD4 but not the CD8 response. The use of inactivated SARS virus with MF59 enhanced the CD4 and antibody response even after gene-based vaccination. Because both cellular and humoral immune responses are generated by gene-based vaccination and inactivated viral boosting, this strategy may prove useful in the generation of SARS-CoV vaccines.


Parasitology ◽  
2017 ◽  
Vol 144 (9) ◽  
pp. 1191-1202 ◽  
Author(s):  
JORDANNA LUÍZA DE LIMA CELESTE ◽  
ANA PAULA VENUTO MOURA ◽  
JOÃO CARLOS FRANÇA-SILVA ◽  
GABRIELA MATOS DE SOUSA ◽  
SORAIA OLIVEIRA SILVA ◽  
...  

SUMMARYIn South America, visceral leishmaniasis is frequently caused byLeishmania infantumand, at an unknown frequency, byLeishmania amazonensis. Therefore, mixed infections with these organisms are possible. Mixed infections might affect the clinical course, immune response, diagnosis, treatment and epidemiology of the disease. Here we describe the clinical course of mixed infections withL. amazonensisandL. infantumin a hamster model. We show that mixed infections are associated with more severe clinical disease than infection withL. amazonensisorL. infantumalone. In spleens with mixed infections,L. infantumoutcompetedL. amazonensisin the tissue, but not in culture from tissue. We found increased levels of IgG in animals infected withL. infantum.Although more than 30 bands were revealed in a Western blot, the highest immunogenicity was observed with proteins having molecular masses of 95 and 90 kDa, whereas proteins with molecular masses of lower than 50 kDa were reactive frequently with serum from hamsters infected withL. amazonensis, and proteins with molecular masses of 80 and 70 kDa were reactive only with serum from hamsters infected withL. infantum. This finding has important implications regarding the biology ofLeishmaniaand humoral immune responses to infections with these organisms.


2015 ◽  
Vol 23 (1) ◽  
pp. 2-5 ◽  
Author(s):  
Steven M. Singer

ABSTRACTFor years, studies of the immune response toGiardia lambliainfection focused on the production of IgA by infected hosts and antigenic variation by the parasite to escape destruction by this IgA. A new study by Hanevik and colleagues (C. S. Saghaug, S. Sørnes, D. Peirasmaki, S. Svärd, N. Langeland, and K. Hanevik, Clin Vaccine Immunol 23:11–18, 2016,http://dx.doi.org/10.1128/CVI.00419-15) highlights the emerging role of interleukin-17 (IL-17) in immunity to this parasite. Along with recent studies ofGiardiainfections of animals, this work shows that IL-17 appears to be essential for the control of these infections and to be a key factor linking cellular and humoral immune responses.


Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1293
Author(s):  
Fei Hao ◽  
Xing Xie ◽  
Maojun Liu ◽  
Li Mao ◽  
Wenliang Li ◽  
...  

Caprine herpesvirus 1 (CpHV-1) is a member of the alpha subfamily of herpesviruses, which is responsible for genital lesions and latent infections in goat populations worldwide. In this study, for the first time, the transcriptome and proteomics of CpHV-1 infected Madin Darby bovine kidney (MDBK) cells were explored using RNA-Sequencing (RNA-Seq) and isobaric tags for relative and absolute quantitation-liquid chromatography tandem mass spectrometry (iTRAQ-LC-MS/MS) technology, respectively. RNA-Seq analysis revealed 81 up-regulated and 19 down-regulated differentially expressed genes (DEGs) between infected and mock-infected MDBK cells. Bioinformatics analysis revealed that most of these DEGs were mainly involved in the innate immune response, especially the interferon stimulated genes (ISGs). Gene Ontology (GO) enrichment analysis results indicated that the identified DEGs were significantly mainly enriched for response to virus, defense response to virus, response to biotic stimulus and regulation of innate immune response. Viral carcinogenesis, the RIG-I-like receptor signaling pathway, the cytosolic DNA-sensing pathway and pathways associated with several viral infections were found to be significantly enriched in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database. Eleven selected DEGs (Mx1, RSAD2, IFIT1, IFIT2, IFIT5, IFIH1, IFITM3, IRF7, IRF9, OAS1X and OAS1Y) associated with immune responses were selected, and they exhibited a concordant direction both in RNA-Seq and quantitative real-time RT-PCR analysis. Proteomic analysis also showed significant up-regulation of innate immunity-related proteins. GO analysis showed that the differentially expressed proteins were mostly enriched in defense response and response to virus, and the pathways associated with viral infection were enriched under KEGG analysis. Protein-protein interaction network analysis indicated most of the DEGs related to innate immune responses, as DDX58(RIG-I), IFIH1(MDA5), IRF7, Mx1, RSAD2, OAS1 and IFIT1, were located in the core of the network and highly connected with other DGEs. Our findings support the notion that CpHV-1 infection induced the transcription and protein expression alterations of a series of genes related to host innate immune response, which helps to elucidate the resistance of host cells to viral infection and to clarify the pathogenesis of CpHV-1.


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