scholarly journals Rapid Virus Dissemination in Infant Macaques after Oral Simian Immunodeficiency Virus Exposure in the Presence of Local Innate Immune Responses

2006 ◽  
Vol 80 (13) ◽  
pp. 6357-6367 ◽  
Author(s):  
Kristina Abel ◽  
Bapi Pahar ◽  
Koen K. A. Van Rompay ◽  
Linda Fritts ◽  
Clarissa Sin ◽  
...  
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Simian Immunodeficiency Virus ◽  
Virus Replication ◽  
Proinflammatory Cytokines ◽  
Innate Immune ◽  
Lymphoid Tissues ◽  
Innate Immune Responses ◽  
Virus Dissemination ◽  
Immunodeficiency Virus

ABSTRACT A vaccine to protect human immunodeficiency virus (HIV)-exposed infants is an important goal in the global fight against the HIV pandemic. Two major challenges in pediatric HIV vaccine design are the competence of the neonatal/infant immune system in comparison to the adult immune system and the frequent exposure to HIV via breast-feeding. Based on the hypothesis that an effective vaccine needs to elicit antiviral immune responses directly at the site of virus entry, the pattern of virus dissemination in relation to host immune responses was determined in mucosal and lymphoid tissues of infant macaques at 1 week after multiple oral exposures to simian immunodeficiency virus (SIV). The results show that SIV disseminates systemically by 1 week. Infant macaques can respond rapidly to virus challenge and mount strong innate immune responses. However, despite systemic infection, these responses are most pronounced in tissues close to the viral entry site, with the tonsil being the primary site of virus replication and induction of immune responses. Thus, distinct anatomic compartments are characterized by unique cytokine gene expression patterns. Importantly, the early response at mucosal entry sites is dominated by the induction of proinflammatory cytokines, while cytokines with direct antiviral activity, alpha/beta interferons, are only minimally induced. In contrast, both antiviral and proinflammatory cytokines are induced in lymphoid tissues. Thus, although infant macaques can respond quickly to oral viral challenge, the locally elicited immune responses at mucosal entry sites are likely to favor immune activation and thereby virus replication and are insufficient to limit virus replication and dissemination.

scholarly journals Lymphatic Dissemination of Simian Immunodeficiency Virus after Penile Inoculation

2016 ◽  
Vol 90 (8) ◽  
pp. 4093-4104 ◽  
Author(s):  
Zhong-Min Ma ◽  
Joseph Dutra ◽  
Linda Fritts ◽  
Christopher J. Miller
Keyword(s):  
Immune Responses ◽  
Lymph Nodes ◽  
Simian Immunodeficiency Virus ◽  
Virus Replication ◽  
Target Cells ◽  
Lymphoid Tissues ◽  
Inguinal Lymph Nodes ◽  
Mucosal Surfaces ◽  
Immunodeficiency Virus ◽  
Rna Levels

ABSTRACTThe human immunodeficiency virus (HIV) is primarily transmitted by heterosexual contact, and approximately equal numbers of men and women worldwide are infected with the virus. Understanding the biology of HIV acquisition and dissemination in men exposed to the virus by insertive penile intercourse is likely to help with the rational design of vaccines that can limit or prevent HIV transmission. To characterize the target cells and dissemination pathways involved in establishing systemic simian immunodeficiency virus (SIV) infection, we necropsied male rhesus macaques at 1, 3, 7, and 14 days after penile SIV inoculation and quantified the levels of unspliced SIV RNA and spliced SIV RNA in tissue lysates and the number of SIV RNA-positive cells in tissue sections. We found that penile (glans, foreskin, coronal sulcus) T cells and, to a lesser extent, macrophages and dendritic cells are primary targets of infection and that SIV rapidly reaches the regional lymph nodes. At 7 days after inoculation, SIV had disseminated to the blood, systemic lymph nodes, and mucosal lymphoid tissues. Further, at 7 days postinoculation (p.i.), spliced SIV RNA levels were the highest in the genital lymph nodes, indicating that this is the site where the infection is initially amplified. By 14 days p.i., spliced SIV RNA levels were high in all tissues, but they were the highest in the gastrointestinal tract, indicating that the primary site of virus replication had shifted from the genital lymph nodes to the gut. The stepwise pattern of virus replication and dissemination described here suggests that vaccine-elicited immune responses in the genital lymph nodes could help prevent infection after penile SIV challenge.IMPORTANCETo be the most effective, vaccines should produce antiviral immune responses in the anatomic sites of virus replication. Thus, understanding the path taken by HIV from the mucosal surfaces, which are the site of virus exposure, to the deeper tissues where the virus replicates will provide insight into where AIDS vaccines should produce immunity to be the most effective. In this study, we determined that, by day 7 after penile inoculation, SIV has moved first to the inguinal lymph nodes and replicates to high levels. Although the virus is widely disseminated to other tissues by day 7, replication is largely limited to the inguinal lymph nodes. The step-by-step movement of SIV from penile mucosal surfaces to the draining lymph nodes may allow an HIV vaccine that produces immunity in these lymph nodes to block HIV from establishing an infection in an exposed person.

scholarly journals Inhibiting pyrimidine biosynthesis impairs Ebola virus replication through depletion of nucleoside pools and activation of innate immune responses

2018 ◽  
Vol 158 ◽  
pp. 288-302 ◽  
Author(s):  
Priya Luthra ◽  
Jacinth Naidoo ◽  
Colette A. Pietzsch ◽  
Sampriti De ◽  
Sudip Khadka ◽  
...  
Keyword(s):  
Immune Responses ◽  
Virus Replication ◽  
Ebola Virus ◽  
Innate Immune ◽  
Pyrimidine Biosynthesis ◽  
Innate Immune Responses

scholarly journals Commensal and Opportunistic Bacteria Present in the Microbiota in Atlantic Cod (Gadus morhua) Larvae Differentially Alter the Hosts’ Innate Immune Responses

2021 ◽  
Vol 10 (1) ◽  
pp. 24
Author(s):  
Ragnhild Inderberg Vestrum ◽  
Torunn Forberg ◽  
Birgit Luef ◽  
Ingrid Bakke ◽  
Per Winge ◽  
...  
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Atlantic Cod ◽  
Innate Immune ◽  
Rrna Gene ◽  
Innate Immune Responses ◽  
Transcriptional Responses ◽  
Gut Morphology ◽  
Germ Free ◽  
Opportunistic Bacteria

The roles of host-associated bacteria have gained attention lately, and we now recognise that the microbiota is essential in processes such as digestion, development of the immune system and gut function. In this study, Atlantic cod larvae were reared under germ-free, gnotobiotic and conventional conditions. Water and fish microbiota were characterised by 16S rRNA gene analyses. The cod larvae’s transcriptional responses to the different microbial conditions were analysed by a custom Agilent 44 k oligo microarray. Gut development was assessed by transmission electron microscopy (TEM). Water and fish microbiota differed significantly in the conventional treatment and were dominated by different fast-growing bacteria. Our study indicates that components of the innate immune system of cod larvae are downregulated by the presence of non-pathogenic bacteria, and thus may be turned on by default in the early larval stages. We see indications of decreased nutrient uptake in the absence of bacteria. The bacteria also influence the gut morphology, reflected in shorter microvilli with higher density in the conventional larvae than in the germ-free larvae. The fact that the microbiota alters innate immune responses and gut morphology demonstrates its important role in marine larval development.

scholarly journals Mitochondria surveillance systems trigger innate immune responses to bacterial pathogens via AMPK pathway in C. elegans

2020 ◽  
Author(s):  
Shouyong Ju ◽  
Hanqiao Chen ◽  
Shaoying Wang ◽  
Jian Lin ◽  
Raffi V Aroian ◽  
...  
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Innate Immune ◽  
Surveillance Systems ◽  
Innate Immune Responses ◽  
Energy Status ◽  
Microbial Infection ◽  
C Elegans ◽  
Host Interaction ◽  
Intracellular Energy

AbstractPathogen recognition and triggering pattern of host innate immune system is critical to understanding pathogen-host interaction. It is generally accepted that the microbial infection can be recognized by host via pattern-triggered immunity (PTI) or effector-triggered immunity (ETI) responses. Recently, non-PRR-mediated cellular surveillance systems have been reported as an important supplement strategy to PTI and ETI responses. However, the mechanism of how surveillance systems sense pathogens and trigger innate immune responses is largely unknown. In the present study, using Bacillus thuringiensis-Caenorhabditis elegans as a model, we found a new approach for surveillance systems to sense the pathogens through no-PPRs patterns. We reported C. elegans can monitor intracellular energy status through the mitochondrial surveillance system to triggered innate immune responses against pathogenic attack via AMP-activated protein kinase (AMPK). Consider that the mitochondria surveillance systems and AMPK are conserved components from worms to mammals, our study suggests that disrupting mitochondrial homeostasis to activate the immune system through AMPK-dependent pathways may widely existing in animals.

scholarly journals The neuropeptide receptor NMUR-1 regulates the specificity of C. elegans innate immunity against pathogen infection

2021 ◽  
Author(s):  
Phillip Wibisono ◽  
Shawndra Wibisono ◽  
Jan Watteyne ◽  
Chia-Hui Chen ◽  
Durai Sellegounder ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Immune System ◽  
Immune Responses ◽  
Adaptive Immune System ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Immune Genes ◽  
C Elegans ◽  
Adaptive Immune ◽  
Functional Assays

A key question in current immunology is how the innate immune system generates high levels of specificity. Like most invertebrates, Caenorhabditis elegans does not have an adaptive immune system and relies solely on innate immunity to defend itself against pathogen attacks, yet it can still differentiate different pathogens and launch distinct innate immune responses. Here, we have found that functional loss of NMUR-1, a neuronal GPCR homologous to mammalian receptors for the neuropeptide neuromedin U, has diverse effects on C. elegans survival against various bacterial pathogens. Transcriptomic analyses and functional assays revealed that NMUR-1 modulates C. elegans transcription activity by regulating the expression of transcription factors, which, in turn, controls the expression of distinct immune genes in response to different pathogens. Our study has uncovered a molecular basis for the specificity of C. elegans innate immunity that could provide mechanistic insights into understanding the specificity of vertebrate innate immunity.

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