scholarly journals The effects of host heterogeneity on pathogen population structure

1999 ◽  
Vol 354 (1384) ◽  
pp. 711-719 ◽  
Author(s):  
Sunetra Gupta ◽  
Alison Galvani
Keyword(s):  
Immune Responses ◽  
High Frequency ◽  
Host Population ◽  
Immune Selection ◽  
Pathogen Population ◽  
Host Immune Responses ◽  
Wide Range ◽  
Specific Manner ◽  
Variable Antigen ◽  
The Individual

We have shown that among pathogens, populations may self–organize into strains with non–overlapping repertoires of antigenic variants as a consequence of strong immune selection operating on polymorphic antigens. Recently, we have also demonstrated that over a wide range of intermediate levels of immune selection, pathogens may still be structured into discrete strains, but different sets of non–overlapping pathogen types will replace each other in a cyclical or chaotic manner. These models assume that the ranking of antigens in terms of the strength of the induced immune response is the same for every host. However, host immune responses may be restricted by the genotype of the individual. To explore this issue, a mathematical model was constructed under the assumption that a proportion of the host population responds principally to a variable antigen while the remainder of the population responds principally to a conserved antigen. The results of this analysis indicate that discrete strain structure (DSS) will be maintained even with a high frequency of hosts that do not respond in a variant–specific manner. Furthermore, the range of the immune selection pressure over which DSS prevails is increased (and the region of cyclical or chaotic behaviour reduced) by the inclusion of hosts that respond in a cross–reactive rather than a variant–specific manner.

scholarly journals Linking the antigen archive structure to pathogen fitness in African trypanosomes

2013 ◽  
Vol 280 (1753) ◽  
pp. 20122129 ◽  
Author(s):  
Erida Gjini ◽  
Daniel T. Haydon ◽  
J. D. Barry ◽  
Christina A. Cobbold
Keyword(s):  
Immune Responses ◽  
Antigenic Variation ◽  
Molecular Level ◽  
Host Population ◽  
Molecular Processes ◽  
Pathogen Population ◽  
African Trypanosomes ◽  
Host Immune Responses ◽  
Selective Pressures ◽  
Pathogen Fitness

Systems that generate antigenic variation enable pathogens to evade host immune responses and are intricately interwoven with major pathogen traits, such as host choice, growth, virulence and transmission. Although much is understood about antigen switching at the molecular level, little is known about the cross-scale links between these molecular processes and the larger-scale within and between host population dynamics that they must ultimately drive. Inspired by the antigenic variation system of African trypanosomes, we apply modelling approaches to our expanding understanding of the organization and expression of antigen repertoires, and explore links across these scales. We predict how pathogen population processes are determined by underlying molecular genetics and infer resulting selective pressures on important emergent repertoire traits.

scholarly journals The generation of influenza outbreaks by a network of host immune responses against a limited set of antigenic types

2007 ◽  
Vol 104 (18) ◽  
pp. 7711-7716 ◽  
Author(s):  
Mario Recker ◽  
Oliver G. Pybus ◽  
Sean Nee ◽  
Sunetra Gupta
Keyword(s):  
Immune Responses ◽  
Alternative Explanation ◽  
Host Population ◽  
Functional Constraints ◽  
Immune Selection ◽  
Host Immune Responses ◽  
Population Immunity ◽  
Viral Mutation ◽  
Influenza Outbreaks ◽  
Antigenic Type

It is commonly believed that influenza epidemics arise through the incremental accumulation of viral mutations, culminating in a novel antigenic type that is able to escape host immunity. Successive epidemic strains therefore become increasingly antigenically distant from a founding strain. Here, we present an alternative explanation where, because of functional constraints on the defining epitopes, the virus population is characterized by a limited set of antigenic types, all of which may be continuously generated by mutation from preexisting strains and other processes. Under these circumstances, influenza outbreaks arise as a consequence of host immune selection in a manner that is independent of the mode and tempo of viral mutation. By contrast with existing paradigms, antigenic distance between epidemic strains does not necessarily accumulate with time in our model, and it is the changing profile of host population immunity that creates the conditions for the emergence of the next influenza strain rather than the mutational capabilities of the virus.

scholarly journals The DBL-1/TGF-β signaling pathway regulates pathogen-specific innate immune responses in C. elegans

2021 ◽  
Author(s):  
Bhoomi Madhu ◽  
Tina L. Gumienny
Keyword(s):  
Innate Immunity ◽  
Immune Responses ◽  
Signaling Pathway ◽  
Defense Responses ◽  
C Elegans ◽  
Host Immune Responses ◽  
Wide Range ◽  
Independent Functions ◽  
Multiple Cell

Innate immunity in animals is orchestrated by multiple cell signaling pathways, including the TGF-β; superfamily pathway. While the role of TGF-β signaling in innate immunity has been clearly identified, the requirement for this pathway in generating specific, robust responses to different bacterial challenges has not been characterized. Here, we address the role of DBL-1/TGF-β in regulating signature host defense responses to a wide range of bacteria in C. elegans. This work reveals a role of DBL-1/TGF-β in animal survival, organismal behaviors, and molecular responses in different environments. Additionally, we identify a novel role for SMA-4/Smad that suggests both DBL-1/TGF-β-dependent and -independent functions in host avoidance responses. RNA-seq analyses and immunity reporter studies indicate DBL-1/TGF-β differentially regulates target gene expression upon exposure to different bacteria. Furthermore, the DBL-1/TGF-β pathway is itself differentially affected by the bacteria exposure. Collectively, these findings demonstrate bacteria-specific host immune responses regulated by the DBL-1/TGF-β signaling pathway.

scholarly journals Transcriptome Analysis of Mouse Brain Infected with Toxoplasma gondii

2013 ◽  
Vol 81 (10) ◽  
pp. 3609-3619 ◽  
Author(s):  
Sachi Tanaka ◽  
Maki Nishimura ◽  
Fumiaki Ihara ◽  
Junya Yamagishi ◽  
Yutaka Suzuki ◽  
...  
Keyword(s):  
Gene Expression ◽  
Toxoplasma Gondii ◽  
Immune Responses ◽  
Mouse Brain ◽  
Transcriptome Analysis ◽  
Host Cells ◽  
Content Type ◽  
Host Immune Responses ◽  
Wide Range ◽  
The Brain

ABSTRACTToxoplasma gondiiis an obligate intracellular parasite that invades a wide range of vertebrate host cells. Chronic infections withT. gondiibecome established in the tissues of the central nervous system, where the parasites may directly or indirectly modulate neuronal function. However, the mechanisms underlying parasite-induced neuronal disorder in the brain remain unclear. This study evaluated host gene expression in mouse brain following infection withT. gondii. BALB/c mice were infected with the PLK strain, and after 32 days of infection, histopathological lesions in the frontal lobe were found to be more severe than in other areas of the brain. Total RNA extracted from infected and uninfected mouse brain samples was subjected to transcriptome analysis using RNA sequencing (RNA-seq). In theT. gondii-infected mice, 935 mouse brain genes were upregulated, whereas 12 genes were downregulated. GOstat analysis predicted that the upregulated genes were primarily involved in host immune responses and cell activation. Positive correlations were found between the numbers of parasites in the infected mouse brains and the expression levels of genes involved in host immune responses. In contrast, genes that had a negative correlation with parasite numbers were predicted to be involved in neurological functions, such as small-GTPase-mediated signal transduction and vesicle-mediated transport. Furthermore, differential gene expression was observed between mice exhibiting the clinical signs of toxoplasmosis and those that did not. Our findings may provide insights into the mechanisms underlying neurological changes duringT. gondiiinfection.

Factors affecting the evolution of virulence: nematode parasites of fig wasps as a case study

Parasitology ◽  
1995 ◽  
Vol 111 (S1) ◽  
pp. S179-S191 ◽  
Author(s):  
E. A. Herre
Keyword(s):  
Horizontal Transmission ◽  
Host Population ◽  
Lifetime Reproductive Success ◽  
Evolutionary Relationships ◽  
Parameter Estimates ◽  
Fig Wasps ◽  
Evolution Of Virulence ◽  
Wide Range ◽  
The Individual ◽  
Host Parasite

SUMMARYThe natural history of fig-pollinating wasps and their associated species-specific nematodes allows the measurement of many parameters which are relevant to testing hypotheses concerning host-parasite ecology and evolution. Within fig wasps species, it is possible to estimate lifetime reproductive success of foundress wasps as a function of presence or absence of nematode parasitism (virulence). Across species, there is a wide range of host population structures which, in turn, results in a range of opportunities for either horizontal or vertical nematode transmission. Therefore, estimates of virulence can be related to opportunities for transmission across a group of closely related hosts and their parasites. Further, the dynamics of the nematode infections over ecological and short-term evolutionary timescales can be monitored, giving added insight into the interpretation of the virulence estimates. Moreover, several scales of longer term evolutionary relationships are either known directly from fossil evidence or can be inferred from molecular data, providing deeper temporal context for the observed patterns. This combination of attributes permits detailed testing of hypotheses concerning the factors that potentially influence the evolution of virulence in host-parasite systems, and further, population and simulation models of the system that incorporate the parameter estimates can clarify the interpretation of how those factors act. There is little evidence suggesting that intermediate and long-term evolutionary relationships explain current levels of virulence. That is, it appears that virulence can change rapidly relative to speciation events, and that the nematodes do not tend to become ‘benign over time’. Instead, it appears that host population structure can influence the evolution of parasite virulence by affecting the relative opportunities for horizontal to vertical transmission, which, in turn, influences the relative costs and benefits of virulence to the nematodes. At one level, increased opportunities for horizontal transmission decouple the reproductive interests of the individual nematodes from those of the individual hosts that they are directly parasitizing, thereby reducing the cost of virulence to individual nematodes. At another level, increased opportunities of horizontal transmission also increases the relative frequency of hosts infected by multiple strains of nematodes. This promotes the evolution of more virulent forms by increasing the relative importance of within-host competition among nematode strains, thereby favouring strains that ‘eat more host sooner’. An interesting property of the fig-nematode systems is that the proportion of infected hosts does not change dramatically through time. This finding implies that there can be considerable negative effects on survival of infected hosts in addition to the previously documented reductions in fecundity of infected foundresses, because the latter are insufficient to account for the observed stability of wasp infection rates.

Optimality analysis of Th1/Th2 immune responses during microparasite-macroparasite co-infection, with epidemiological feedbacks

Parasitology ◽  
2008 ◽  
Vol 135 (7) ◽  
pp. 841-853 ◽  
Author(s):  
ANDY FENTON ◽  
TRACEY LAMB ◽  
ANDREA L. GRAHAM
Keyword(s):  
Immune Responses ◽  
Population Level ◽  
Parasite Abundance ◽  
Individual Level ◽  
Host Immune Responses ◽  
Individual Host ◽  
Diverse Community ◽  
The Individual ◽  
Optimality Models

SUMMARYIndividuals are typically co-infected by a diverse community of microparasites (e.g. viruses or protozoa) and macroparasites (e.g. helminths). Vertebrates respond to these parasites differently, typically mounting T helper type 1 (Th1) responses against microparasites and Th2 responses against macroparasites. These two responses may be antagonistic such that hosts face a ‘decision’ of how to allocate potentially limiting resources. Such decisions at the individual host level will influence parasite abundance at the population level which, in turn, will feed back upon the individual level. We take a first step towards a complete theoretical framework by placing an analysis of optimal immune responses under microparasite-macroparasite co-infection within an epidemiological framework. We show that the optimal immune allocation is quantitatively sensitive to the shape of the trade-off curve and qualitatively sensitive to life-history traits of the host, microparasite and macroparasite. This model represents an important first step in placing optimality models of the immune response to co-infection into an epidemiological framework. Ultimately, however, a more complete framework is needed to bring together the optimal strategy at the individual level and the population-level consequences of those responses, before we can truly understand the evolution of host immune responses under parasite co-infection.

scholarly journals TICK SALIVA TOXINS, HOST IMMUNE RESPONSES AND ITS BIOLOGICAL EFFECTS

2021 ◽  
pp. 9-19
Author(s):  
NIDHI YADAV ◽  
RAVI KANT UPADHYAY
Keyword(s):  
Immune Responses ◽  
Biological Effects ◽  
Immune Therapy ◽  
Economic Losses ◽  
Tick Saliva ◽  
Tropical Regions ◽  
Terrestrial Vertebrates ◽  
Host Immune Responses ◽  
Blood Sucking ◽  
Wide Range

Ticks are the most important ancient group of obligate blood-sucking ectoparasites of terrestrial vertebrates mainly of livestock. These small-sized animals are found in tropical and sub-tropical regions of the world. These act as vectors and transmit a wide range of protozoa, bacteria and viruses tick-borne diseases. These attach to host skin for blood-sucking and transmit disease pathogens through saliva. Ticks withdraw large volumes of blood from livestock and make them anemic and do significant weight loss. Ticks cause severe economic losses in livestock directly through blood-feeding and indirectly by transmitting protozoan, rickettsial and viral diseases This article highlights toxins/proteins secreted in tick saliva, and its important biological effects like anti-inflammatory, immunosuppressant peptide, and immunomodulatory and anti-chemokine activities. The present article clears host-pathogen interactions and invasion of a host by ticks, biological effects of tick saliva toxins and its host immune responses. These toxins could be used as immunoreactive proteins as a prerequisite for the development of specific and sensitive immunoassays for the determination of tick-borne illness. The authors suggest important management strategies for successful control of cattle, bird and canine ticks. This article also suggests tick control methods such as physical, chemical, hormonal and including prophylactic use of antibody and vaccine immune therapy.

scholarly journals A Perspective on the Emergence of Sialic Acids as Potent Determinants Affecting Leishmania Biology

2011 ◽  
Vol 2011 ◽  
pp. 1-14 ◽  
Author(s):  
Angana Ghoshal ◽  
Chitra Mandal
Keyword(s):  
Nitric Oxide ◽  
Immune Responses ◽  
Sialic Acids ◽  
Differential Distribution ◽  
Host Immune Responses ◽  
Wide Range ◽  
Leishmania Spp ◽  
Parasite Biology ◽  
Vertebrate Hosts

Leishmaniasis caused by Leishmania sp. has a wide range of manifestations from cutaneous to the deadly visceral form. They shuttle between the invertebrate and vertebrate hosts as promastigotes and amastigotes having adaptations for subverting host immune responses. Parasite-specific glycoconjugates have served as important determinants influencing parasite recognition, internalization, differentiation, multiplication, and virulence. Despite the steady progress in the field of parasite glycobiology, sialobiology has been a less traversed domain of research in leishmaniasis. The present paper focuses on identification, characterization, and differential distribution of sialoglycotope having the linkage-specific 9-O-acetylated sialic acid in promastigotes of different Leishmania sp. causing different clinical ramifications emphasizing possible role of these sialoglycotopes in infectivity, virulence, nitric oxide resistance, and host modulation in Leishmania spp. asserting them to be important molecules influencing parasite biology.

scholarly journals Comparative Evaluation of the Vaccine Efficacies of Three Adenovirus-Based Vector Types in the Friend Retrovirus Infection Model

2019 ◽  
Vol 93 (21) ◽  
Author(s):  
Camilla Patrizia Hrycak ◽  
Sonja Windmann ◽  
Wibke Bayer
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Cross Reactivity ◽  
Infection Model ◽  
Friend Retrovirus ◽  
Wide Range ◽  
The Individual ◽  
High Level ◽  
Cellular Immune

ABSTRACT Adenovirus (AdV)-based vectors are popular experimental vaccine vectors, but despite their ability to induce strong immune responses, their application is impeded by widespread preexisting immunity against many AdV types that can impair or even abrogate the induction of transgene-specific immune responses. Therefore, the development of vectors based on AdV types with a low seroprevalence is important for effective AdV-based immunization in humans. We investigated the immunization efficacy of vectors based on AdV type 48 (Ad48) and Ad50 in the ovalbumin (ova) model as well as the Friend retrovirus (FV) model, which allows testing of the protective effect of vaccine-induced immunity. Using ova-encoding vectors, we found a significantly lower induction of ova-specific CD8+ T cells and antibody responses by Ad48- and Ad50-based vectors than by Ad5-based vectors. Similarly, we found a reduced induction of FV-specific CD8+ T cell responses in Ad48- and Ad50.Leader-Gag-immunized mice compared with that in Ad5-immunized mice; however, some of those mice were able to control the FV infection, and protection correlated with the level of neutralizing antibodies 10 days after FV challenge. Analyses of the AdV-specific antibodies and CD8+ T cells induced by the individual AdV types revealed a high level of cross-reactivity, and the efficacy of Ad48-based immunization was impaired in Ad5-preimmune mice. Our results show that the immunity induced by Ad48- and Ad50-based vectors is reduced compared to that induced by Ad5 and is sufficient to control FV infection in only some of the immunized mice. A high level of cross-reactivity suggests that AdV preimmunity must be considered even when applying rare AdV-based vectors. IMPORTANCE AdV-based vectors are important tools for the development of vaccines against a wide range of pathogens. While AdV vectors are generally considered safe and highly effective, their application can be severely impaired by preexisting immunity due to the widespread seroprevalence of some AdV types. The characterization of different AdV types with regard to immunogenicity and efficacy in challenge models is of great importance for the development of improved AdV-based vectors that allow for efficient immunization despite anti-AdV immunity. We show that the immunity induced by an Ad48-based vector is inferior to that induced by an Ad5-based vector but can still mediate the control of an FV infection in highly FV-susceptible mice. However, the efficacy of Ad48-based immunization was impaired in Ad5-preimmune mice. Importantly, we found cross-reactivity of both the humoral and cellular immune responses raised by the individual AdV types, suggesting that switching to a different AdV type may not be sufficient to circumvent preexisting anti-AdV immunity.

scholarly journals New Insights on the Early Interaction Between Typhoid and Non-typhoid Salmonella Serovars and the Host Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Bárbara M. Schultz ◽  
Felipe Melo-Gonzalez ◽  
Geraldyne A. Salazar ◽  
Bárbara N. Porto ◽  
Claudia A. Riedel ◽  
...  
Keyword(s):  
Immune Responses ◽  
Mouse Models ◽  
Host Cells ◽  
Common Source ◽  
Bacterial Burden ◽  
Host Immune Responses ◽  
Wide Range ◽  
Animal Hosts ◽  
Early Interaction ◽  
Water Borne

Salmonella enterica is a common source of food and water-borne infections, causing a wide range of clinical ailments in both human and animal hosts. Immunity to Salmonella involves an interplay between different immune responses, which are rapidly initiated to control bacterial burden. However, Salmonella has developed several strategies to evade and modulate the host immune responses. In this sense, the main knowledge about the pathogenicity of this bacterium has been obtained by the study of mouse models with non-typhoidal serovars. However, this knowledge is not representative of all the pathologies caused by non-typhoidal serovars in the human. Here we review the most important features of typhoidal and non-typhoidal serovars and the diseases they cause in the human host, describing the virulence mechanisms used by these pathogens that have been identified in different models of infection.

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