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opencc-zeroMay 2024View details →

A model of within-host interactions between host resources, macroparasite infection and immune response

This project was designed to mathematically investigate the of different host parasite-mitigation strategies on host condition. The R code herein comprises: <ul> <li>An ODE model of within-host interactions between a macroparasite (e.g. helminth) infection, host resource levels and host immune response, and the consequent effects on host condition. In brief, resources are ingested and utilised by the host, leading to inceased condition. The host is infected by a parasite, which matures and establishes within the host; both age stages cause harm to the host, decreasing host condition. The presence of the parasite stimulates an immune response, which can either target larval or adult parasites (a resistance strategy), or ameliorate the harm they cause (a tolerance strategy). The host can also reduce resource intake in order to also reduce ingestion of parasite infective stages (an avoidance strategy). Resistance responses have an associated immunopathology, in that the immune response also harms the host.</li> <li>Code to plot model trajectories over time.</li> <li>Code to plot multiple trajectories as a heat map, in which the x-axis is time and the y-axis is a parameter representing the host investment in its parasite-mitigation strategy.</li> <li>Code to calculate the optimum host investment for each strategy, over various sets of parameter values, as determined by maximising mean host condition over a given timeframe, and to plot the output.</li> <li>The same are also provided for an ODE model in which the total immune response is allocated between the two resistance responses and tolerance (a combined strategy). The optimisation code optimises both the total investment in immune repsonse, and how much is allocated to the three different individual strategies.</li> </ul> The model and results are described in detail in the associated manuscript. We also provide here the simulated datasets in which the optimum host investments were calculated over a range of different parameter values, as these take several hours to run on a standard desktop computer..

Fig. 2 in Experimental evaluation of pathogenicity and acquired immunity of Eimeria species, E. uekii and E. raichoi, infecting Japanese rock ptarmigans in a subspecies of the birds

Fig. 2. The number of oocysts per gram of feces (OPG) after inoculation with E. uekii and E. raichoi oocysts. Panels A and B show E. uekii and E. raichoi OPG, respectively. Chicks Nos. 1–3 were inoculated depending on the manner of oocysts E. uekii and E. raichoi as described at the bottom of Figure, and mouse no. 4 was inoculated with oocysts of E. raichoi.

Fig. 1 in Experimental evaluation of pathogenicity and acquired immunity of Eimeria species, E. uekii and E. raichoi, infecting Japanese rock ptarmigans in a subspecies of the birds

Fig. 1. Weight gain of Svalbard rock ptarmigans after inoculation with E. uekii and E. raichoi oocysts. The inoculation doses of E. uekii and E. raichoi were 4 104 and × 17 103 or 4 103 (A), 2 104 and 8 103 (B), 4 103 and 17 or 4 102 (C), and 4 102 and 17 or 4 101 (D), respectively. Group E was administered PBS as a × × × × × × × × control, and group F was inoculated with 4 104 oocysts of E. raichoi that had been passed in turkeys. "n" indicates the numbers of examined chicks.

Fig. 5 in Experimental evaluation of pathogenicity and acquired immunity of Eimeria species, E. uekii and E. raichoi, infecting Japanese rock ptarmigans in a subspecies of the birds

Fig. 5. Histopathological photomicrographs of sections of the intestines of challenged chicks. Panels A and B show the ileum and duodenum of the primary inoculated chick at 7 days PI, respectively. Panels C and D show the ileum and colon of a non-inoculated chick at 7 days PI, respectively. Arrows indicate developmental zoites (sexual stages in panels C and D). Scale bars are 20 μm in panels A and C and 50 μm in panels B and D.

Fig. 4 in Experimental evaluation of pathogenicity and acquired immunity of Eimeria species, E. uekii and E. raichoi, infecting Japanese rock ptarmigans in a subspecies of the birds

Fig. 4. Weight gain of Svalbard rock ptarmigans after challenge inoculation. Panels A and B show the weight of control (PBS) and primary inoculated chicks, respectively. Two-direction arrows indicate the period of challenge inoculation, 4 104 E. uekii and 2 103 E. raichoi for 5 days.

Fig. 3 in Experimental evaluation of pathogenicity and acquired immunity of Eimeria species, E. uekii and E. raichoi, infecting Japanese rock ptarmigans in a subspecies of the birds

Fig. 3. Histopathological photomicrographs of sections from an experimentally inoculated chick (Svalbard rock ptarmigan). Panel A shows the ileum of the chick at 4 days PI after inoculation with 4 × 104 E. uekii and 2 × 103 E. raichoi oocysts. Panel B is a higher magnification of the section. Arrows indicate developmental zoites or mature schizonts (in panel B). Scale bars in panels A and B are 20 μm and 50 μm, respectively.

opencc-by-4.0Aug 2024View details →

Data for milk immune factors/nutrients and infection

Data for milk immune factors/nutrients and infection   Important Information This file (Milk_immune_factors-nutrients&infection_data) contains the dataset used for the journal article manuscript entitled, "Lactose in human milk is associated with lower rates of infection during a drought" by Fujita and Wander. This manuscript is under review for publication as of August, 2024. The variables and data are found under the data tab, and the data coding information in the info & code tab.   Please contact Masako Fujita (ORCID 0000-0001-9173-6678, E-mail masakof@msu.edu) for questions regarding the data.   Condition for data use: Please cite DOI: 10.5281/zenodo.13377353 for this data file and the article, and acknowledge the support from the grant agencies listed below:   Data source/article: <ul> <li> Fujita M. 2024. Data for milk immune factors/nutrients and infection. DOI:  10.5281/zenodo.13377353.</li> <li> Fujita M, Wander K. [Year] Lactose in human milk is associated with lower rates of infection during a drought. [Journal name, article DOI].</li> </ul>   Grant support: <ul> <li>National Science Foundation (BCS-0622358, BCS-1638167) </li> <li>Wenner-Gren Foundation (Gr. 7460, Gr. 9278) </li> </ul>

opencc-by-4.0Aug 2024View details →

Hepatic transcriptomic analysis reveals differential regulation of metabolic and immune pathways in three strains of chickens with distinct growth rate exposed to mixed parasites infections

This dataset was generated from the study investigating hepatic gene expression in three strains of chickens: Ross-308 (R), Lohmann Brown Plus (LB), and Lohmann Dual (LD), 2 weeks after either an experimental infection (n = 18) with both A. galli and H. gallinarum or kept as uninfected control (n = 12).

opencc-zeroAug 2023View details →

A simulated natural heatwave perturbs bumble bee immunity and resistance to infection

As a consequence of ongoing climate change, heatwaves are predicted to increase in frequency, intensity, and duration in many regions. Such extreme events can shift organisms from thermal optima for physiology and behavior, with the thermal stress hypothesis predicting reduced performance at temperatures where the maintenance of biological functions is energetically costly. Performance includes the ability to resist biotic stressors, such as infectious diseases. Climate change is a proposed threat to native bee pollinators, directly and through indirect effects on floral resources, but the thermal stress hypothesis, particularly pertaining to disease resistance, has received limited attention. We exposed adult Bombus impatiens bumble bee workers to simulated, ecologically relevant heatwave or control thermal regimes and assessed longevity, immunity, and resistance to concurrent or future parasite infections. We demonstrate that survival and induced antibacterial immunity are reduced following heatwaves. Supporting that heatwave exposure compromised immunity, the cost of immune activation by a non-pathogenic elicitor was thermal regime dependent, with costs to long-term survival in control but not heatwave exposed bees. However, in the face of real infections, an inability to mount an optimal immune response will be detrimental, which was reflected by higher infections from trypanosome parasite exposure following the heatwave, relative to the control regime. These results demonstrate interactions between heatwave exposure and bumble bee performance, including immune and infection outcomes. Thus, the health of bumble bee pollinator populations may be affected through altered interactions with parasites and pathogens, in addition to other effects of extreme manifestations of climate change.

opencc-by-4.0Sep 2023View details →

Malaria drives unique regulatory responses across multiple immune cells during human infection

To investigate malaria driven transcriptional changes in specific immune cell subsets, we sorted live PBMCs from 6 malaria infected donors (day 0), and two subsequent time points after drug treatment (day 7 and 28), along with PBMCs from 2 healthy controls. We performed scRNAseq of these cells, and used clustering and sub-clustering to identify specific immune cell subsets. Differential gene analysis between day 0 and day 28 was performed for each cell cluster and sub-cluster. Key transcriptional changes were confirmed at the protein level with additional donor samples.

publicMay 2024View details →

A model of within-host interactions between host resources, macroparasite infection and immune response

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publicAug 2023View details →

A simulated natural heatwave perturbs bumble bee immunity and resistance to infection

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opencc-zeroMay 2020View details →

Data from: Single cell RNA-seq analysis reveals that prenatal arsenic exposure results in long-term, adverse effects on immune gene expression in response to Influenza A infection

Arsenic exposure via drinking water is a serious environmental health concern. Epidemiological studies suggest a strong association between prenatal arsenic exposure and subsequent childhood respiratory infections, as well as morbidity from respiratory diseases in adulthood, long after systemic clearance of arsenic. We investigated the impact of exclusive prenatal arsenic exposure on the inflammatory immune response and respiratory health after an adult influenza A (IAV) lung infection. C57BL/6J mice were exposed to 100 ppb sodium arsenite in utero, and subsequently infected with IAV (H1N1) after maturation to adulthood. Assessment of lung tissue and bronchoalveolar lavage fluid (BALF) at various time points post IAV infection reveals greater lung damage and inflammation in arsenic exposed mice versus control mice. Single-cell RNA sequencing analysis of immune cells harvested from IAV infected lungs suggests that the enhanced inflammatory response is mediated by dysregulation of innate immune function of monocyte derived macrophages, neutrophils, NK cells, and alveolar macrophages. Our results suggest that prenatal arsenic exposure results in lasting effects on the adult host innate immune response to IAV infection, long after exposure to arsenic, leading to greater immunopathology. This study provides the first direct evidence that exclusive prenatal exposure to arsenic in drinking water causes predisposition to a hyperinflammatory response to IAV infection in adult mice, which is associated with significant lung damage.

opencc-zeroNov 2020View details →

Prior exposure to long day photoperiods alters immune responses and increases susceptibility to parasitic infection in stickleback

Seasonal disease and parasitic infection are common across organisms, including humans, and there is increasing evidence for intrinsic seasonal variation in immune systems. Changes are orchestrated through organisms' physiological clocks using cues such as day length. Ample research in diverse taxa has demonstrated multiple immune responses are modulated by photoperiod, but to date, there have been few experimental demonstrations that photoperiod cues alter susceptibility to infection. We investigated the interactions among photoperiod history, immunity, and susceptibility in laboratory-bred three-spined stickleback, a long-day breeding fish, and its external, directly-reproducing, monogenean parasite Gyrodactylus gasterostei. We demonstrate that previous exposure to long day photoperiods (PLD) increases susceptibility to infection relative to previous exposure to short days (PSD), and modifies the response to infection for the mucin gene muc2 and Treg cytokine foxp3a in skin tissues in an intermediate 12L:12D photoperiod experimental trial. Expression of skin muc2 is reduced in PLD fish, and negatively associated with parasite abundance. We also observe inflammatory gene expression variation associated with natural inter-population variation in resistance, but find that photoperiod modulation of susceptibility is consistent across host populations. Thus, photoperiod-modulation of the response to infection is important for host susceptibility, highlighting new mechanisms affecting seasonality of host-parasite interactions.

opencc-zeroSep 2019View details →

Data from: Immune stability predicts tuberculosis infection risk in a wild mammal

Immunity is one of the most variable phenotypic traits in animals; however, some individuals may show less fluctuation in immune traits, resulting in stable patterns of immune variation over time. It is currently unknown whether immune variation has consequences for infectious disease risk. In this study, we identified moderately stable immune traits in wild African buffalo and asked whether the stability of these traits affected bovine tuberculosis (TB) infection risk. We found that adaptive immune traits such as the level of IFN-γ released after white blood cell stimulation, the number of circulating lymphocytes, and the level of antibodies against bovine adenovirus-3 were moderately repeatable (i.e. stable) over time, whereas parameters related to innate immunity either had low repeatability (circulating eosinophil numbers) or were not repeatable (e.g. neutrophil numbers, plasma bacteria killing capacity). Intriguingly, individuals with more repeatable IFN-γ and lymphocyte levels were at a significantly higher risk of acquiring TB infection. In stark contrast, average IFN-γ and lymphocyte levels were poor predictors of TB risk, indicating that immune variability rather than absolute response level better captured variation in disease susceptibility. This work highlights the important and under-appreciated role of immune variability as a predictor of infection risk.