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

School of Biological Sciences, University of Liverpool, Biosciences Building, Crown Street, Liverpool, L69 7ZB, UK.
Parasitology (Impact Factor: 2.56). 07/2008; 135(7):841-53. DOI: 10.1017/S0031182008000310
Source: PubMed


Individuals 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.

Download full-text


Available from: Andrew Fenton, Jan 23, 2015
1 Follower
39 Reads
  • Source
    • "The second subgroup of studies modeled population plasticity of Th1/Th2 cell responses. These models included the processes of cross-regulation of Th1/Th2 cell responses either directly by cell-to-cell interactions or via production of Th1/Th2 cytokines (Fishman and Perelson, 1999; Yates et al., 2000, 2004; Bergmann et al., 2001, 2002; Fenton et al., 2008; Eftimie et al., 2010; Groß et al., 2011). Some of these models offered a theoretical explanation of the switch from an initially dominant pathogens-specific Th2 response to a later dominant Th1 response (or vice versa). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Vertebrates are constantly exposed to pathogens, and the adaptive immunity has most likely evolved to control and clear such infectious agents. CD4(+) T cells are the major players in the adaptive immune response to pathogens. Following recognition of pathogen-derived antigens naïve CD4(+) T cells differentiate into effectors which then control pathogen replication either directly by killing pathogen-infected cells or by assisting with generation of cytotoxic T lymphocytes (CTLs) or pathogen-specific antibodies. Pathogen-specific effector CD4(+) T cells are highly heterogeneous in terms of cytokines they produce. Three major subtypes of effector CD4(+) T cells have been identified: T-helper 1 (Th1) cells producing IFN-γ and TNF-α, Th2 cells producing IL-4 and IL-10, and Th17 cells producing IL-17. How this heterogeneity is maintained and what regulates changes in effector T cell composition during chronic infections remains poorly understood. In this review we discuss recent advances in our understanding of CD4(+) T cell differentiation in response to microbial infections. We propose that a change in the phenotype of pathogen-specific effector CD4(+) T cells during chronic infections, for example, from Th1 to Th2 response as observed in Mycobactrium avium ssp. paratuberculosis (MAP) infection of ruminants, can be achieved by conversion of T cells from one effector subset to another (cellular plasticity) or due to differences in kinetics (differentiation, proliferation, death) of different effector T cell subsets (population plasticity). We also shortly review mathematical models aimed at describing CD4(+) T cell differentiation and outline areas for future experimental and theoretical research.
    Frontiers in Physiology 08/2013; 4:206. DOI:10.3389/fphys.2013.00206 · 3.53 Impact Factor
  • Source
    • "Helminths typically induce cytokines associated with a T-helper cell type 2 (Th2) immune response, which simultaneously downregulates T-helper cell type 1 (Th1) cytokines, which are involved in fighting intracellular microparasites [20]. As such, this antagonism may alter co-infection dynamics, and this has been shown to be the case using mathematical models [15], whereas meta-analyses of empirical data have identified key cytokines that may be broadly accountable for shaping co-infection dynamics [13]. It is therefore likely that variation in individual parasite species' establishment, growth and ultimately host infectiousness may be a function of co-infection. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Co-infection by multiple parasites is common within individuals. Interactions between co-infecting parasites include resource competition, direct competition and immune-mediated interactions and each are likely to alter the dynamics of single parasites. We posit that co-infection is a driver of variation in parasite establishment and growth, ultimately altering the production of parasite transmission stages. To test this hypothesis, three different treatment groups of laboratory mice were infected with the gastrointestinal helminth Heligmosomoides polygyrus, the respiratory bacterial pathogen Bordetella bronchiseptica lux(+) or co-infected with both parasites. To follow co-infection simultaneously, self-bioluminescent bacteria were used to quantify infection in vivo and in real-time, while helminth egg production was monitored in real-time using faecal samples. Co-infection resulted in high bacterial loads early in the infection (within the first 5 days) that could cause host mortality. Co-infection also produced helminth 'super-shedders'; individuals that chronically shed the helminth eggs in larger than average numbers. Our study shows that co-infection may be one of the underlying mechanisms for the often-observed high variance in parasite load and shedding rates, and should thus be taken into consideration for disease management and control. Further, using self-bioluminescent bacterial reporters allowed quantification of the progression of infection within the whole animal of the same individuals at a fine temporal scale (daily) and significantly reduced the number of animals used (by 85%) compared with experiments that do not use in vivo techniques. Thus, we present bioluminescent imaging as a novel, non-invasive tool offering great potential to be taken forward into other applications of infectious disease ecology.
    Journal of The Royal Society Interface 03/2013; 10(80):20120588. DOI:10.1098/rsif.2012.0588 · 3.92 Impact Factor
  • Source
    • "Lymphocytes are white blood cells that function within the adaptive immune system, helping to mount antibody-mediated (B cell) and cell-mediated (T cell) responses (Tizard 2004). Because hosts subject to variable environments may exhibit plasticity in their allocation to different immune components—for example, innate versus adaptive, constitutive versus inducible—according to their costs and effectiveness in combating different infectious challenges (Lochmiller and Deerenberg 2000; Klasing 2004; Houston et al. 2007; Bradley and Jackson 2008; Fenton et al. 2008; Martin et al. 2008), we expected that hosts with limited resources may allocate their resources to different forms of immune response. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Mammalian immunology has been studied in great detail in laboratory animals, but few of the tools and less of the insight derived from these studies have been placed in the context of natural, outbred wildlife populations subject to variable environments. We investigated patterns of innate immunity in free-ranging African buffalo in relation to host traits (age, reproductive status, body condition, white blood cell counts) and disease status (bovine tuberculosis [BTB], gastrointestinal nematodes, coccidia, ticks). We evaluated and used an in vitro assay measuring bactericidal competence of blood to assess a component of innate immunity in 200 female buffalo captured at Kruger National Park, South Africa, in June/July and October 2008. Animals with BTB had higher bactericidal competence of blood. Animals with higher neutrophil counts had higher bactericidal competence, whereas animals with lower lymphocyte counts had higher bactericidal competence. This pattern was driven by animals captured at the end of the dry season (October) and may be evidence of immune polarization, whereby individuals are unable to upregulate multiple components of immunity simultaneously. Bactericidal competence did not vary with host pregnancy status, body condition, age, lactation, tick infestation, nematode egg count, or coccidia oocyst count. Overall, we demonstrate that the bactericidal competence assay is practical and informative for field-based studies in wild bovids. Our results also show a correlation between bactericidal competence and bovine tuberculosis infection and reveal possible functional polarizations between different types of immune response in a free-ranging mammal.
    Physiological and Biochemical Zoology 05/2012; 85(3):255-64. DOI:10.1086/665276 · 2.40 Impact Factor
Show more