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Bank voles (Myodes glareolus syn. Clethrionomys glareolus) are frequently used as an animal model in ecological and biomedical studies and are an important reservoir of viral and bacterial zoonotic pathogens, e.g., Puumala hantavirus (PUUV). Here we describe an accidental PUUV outbreak in a large bank vole laboratory colony caused by an accidental introduction of infected wild-trapped bank voles, and the successful eradication of the virus. The eradication plan was based on results of previous studies showing that maternal antibodies (MatAb) protect the young from infection for up to 40 days after weaning, four weeks longer than the estimated duration of PUUV infectivity in the environment. After ensuring that most animals were infected, 620 pairs were mated on the same day. Only females that showed PUUV-specific antibodies and produced offspring within 26 days after mating were retained. All individuals of the parental generation were euthanized before the last weaning. The weaned offspring were moved to individually ventilated cages (IVC) and repeatedly tested for the presence of PUUV-specific antibodies and RNA. A few infected or suspect animals were euthanized. The animals were then mated (in IVC) and, after producing grand-offspring generation, euthanized and tested for PUUV RNA in the lungs. No PUUV RNA was detected, and no animals showed PUUV-specific antibodies in subsequent generations. The successful clearance confirmed the protective efficiency of PUUV-specific MatAb. The procedure for PUUV clearance in the bank vole colony may represent a blueprint for similar approaches in valuable colonies of other rodents infected by similar pathogens.

The nematode Angiostrongylus cantonensis is a rat lungworm, a zoonotic pathogen that causes an emerging infectious disease known as neuroangiostrongyliasis or rat lungworm disease. This study evaluates the efficacy of a vaccine developed for a related species, Angiostrongylus costaricensis, to A. cantonensis in the definitive rat host. Wild-caught rats (Rattus rattus) (n = 28) were mated in captivity to produce uninfected F1 progeny. A total of 43 F1 rats were involved in this trial; 20 non-vaccinated, 21 vaccinated, and two unvaccinated, uninfected. F1 offspring in the vaccinated group were intranasally vaccinated with two doses of PP2 A vaccine, a serine/threonine phosphatase 2 A at a dose of 4 μg vaccine and 4 μg adjuvant/25 g body weight at >3 mos. of age. Unvaccinated rats similarly received 4 μg adjuvant/25 g body weight. Rats were gavaged with 50 L3 stage larvae at ~four weeks post-treatment. Necropsies were conducted at 47–50 days post-live challenge and spleen weight, spleen length, lung and heart weights, and the numbers of worms in heart and lungs were recorded. An average of 23.17 adult worms were found among all F1 rats. We found no significant differences between vaccinated and unvaccinated rats in rat body weight (p = 0.883), spleen weight (p = 0.963), spleen length (p = 0.830), lung weight (p = 0.830), heart weight (p = 0.849), and number of worms in heart and lungs (p = 0.621). A TaqMan™ Custom Array (Applied Biosystems) cytokine assay was used to evaluate gene expression of 12 different cytokines in spleen tissue from 23 rats and no significant differences in cytokine (CT) levels were observed between vaccinated and unvaccinated rats (p values range 0.154–0.988). Thus, the A. costaricensis PP2A vaccine, under these conditions, did not provide adequate protective immunity to guard against infection by A. cantonensis in wild rats.

The human pathogenic nematode Strongyloides stercoralis infects approximately 30–100 million people worldwide. Analysis of the adaptive immune response to S. stercoralis beyond descriptive studies is challenging, as no murine model for the complete infection cycle is available. However, the combined employment of different models each capable of modelling some features of S. stercoralis life cycle and pathology has advanced our understanding of the immunological mechanisms involved in host defence. Here we review: (i) studies using S. stercoralis third stage larvae implanted in diffusion chambers in the subcutaneous tissue of mice that allow analysis of the immune response to the human pathogenic Strongyloides species; (ii) studies using Strongyloides ratti and Strongyloides venezuelensis that infect mice and rats to extend the analysis to the parasites intestinal life stage and (iii) studies using S. stercoralis infected gerbils to analyse the hyperinfection syndrome, a severe complication of human strongyloidiasis that is not induced by rodent specific Strongyloides spp. We provide an overview of the information accumulated so far showing that Strongyloides spp. elicits a classical Th2 response that culminates in different, site specific, effector functions leading to either entrapment and killing of larvae in the tissues or expulsion of parasitic adults from the intestine.

Canine brucellosis, caused by Brucella canis, is a disease of dogs and represents a public health concern as it can be transmitted to humans. Canine brucellosis is on the rise in the United States and there is currently no vaccine for use in dogs. Mice have been extensively utilized to investigate host-pathogen interactions and vaccine candidates for smooth Brucella species and could serve a similar role for studying B. canis. However, comparatively little is known about B. canis infection in mice. The objective of this study was to characterize the kinetics of colonization and pathogenicity of B. canis in mice in order to evaluate the mouse as a model for studying this pathogen. C57BL/6 mice were inoculated intraperitoneally with 105, 107, or 109 CFU of Brucella canis RM6/66 and euthanized 1-, 2-, 4-, 6-, 9-, and 12-weeks post-inoculation. B. canis induced splenomegaly in mice infected with 109 CFU at 1- and 2 weeks post-inoculation while no gross lesions were observed in other dose groups. Infection at the two higher doses resulted in dose-dependent granulomatous hepatitis and histiocytic infiltration of the spleen and mesenteric lymph nodes by 1-2 weeks. B. canis was cultured from the liver, spleen, uterus, bone marrow, lung, and kidney in all groups with colonization declining at a slow but steady rate throughout the experiment. Clearance was achieved by 9 weeks 105 CFU group and by 12 weeks in the 107 CFU group, while B. canis persisted in the spleen until 12 weeks in the highest dose group. Although B. canis does not demonstrate significant replication in C57BL/6 mice, it has the ability to establish an infection, induce splenomegaly, and persist for several weeks in multiple organs. Moreover, 1 x 107 CFU appears to be a suitable challenge dose for investigating vaccine safety.

Capillaria hepatica (syn. for Calodium hepaticum) is a zoonotic nematode parasitizing in the livers of rodents as main hosts and in numerous other mammals including humans. It is the causative agent of the rare conditions of hepatic capillariosis and spurious C. hepatica infections in humans. In this review, 163 reported cases of infestations with this parasite (72 reports of hepatic capillariosis, 13 serologically confirmed infestations and 78 observations of spurious infections) are summarized with an overview on the distribution, symptoms, pathology, diagnosis, serology and therapy of this rare human pathogen.

A subset of atypical memory B cells accumulates in malaria and several infections, autoimmune disorders and aging in both humans and mice. It has been suggested these cells are exhausted long-lived memory B cells, and their accumulation may contribute to poor acquisition of long-lasting immunity to certain chronic infections, such as malaria and HIV. Here, we generated an immunoglobulin heavy chain knock-in mouse with a BCR that recognizes MSP1 of the rodent malaria parasite, Plasmodium chabaudi. In combination with a mosquito-initiated P. chabaudi infection, we show that Plasmodium-specific atypical memory B cells are short-lived and disappear upon natural resolution of chronic infection. These cells show features of activation, proliferation, DNA replication, and plasmablasts. Our data demonstrate that Plasmodium-specific atypical memory B cells are not a subset of long-lived memory B cells, but rather short-lived activated cells, and part of a physiologic ongoing B-cell response.

Sylvatic plague, caused by Yersinia pestis , frequently afflicts prairie dogs ( Cynomys spp.), causing population declines and local extirpations. We tested the effectiveness of bait-delivered sylvatic plague vaccine (SPV) in prairie dog colonies on 29 paired placebo and treatment plots (1–59 ha in size; average 16.9 ha) in 7 western states from 2013 to 2015. We compared relative abundance (using catch per unit effort (CPUE) as an index) and apparent survival of prairie dogs on 26 of the 29 paired plots, 12 with confirmed or suspected plague ( Y. pestis positive carcasses or fleas). Even though plague mortality occurred in prairie dogs on vaccine plots, SPV treatment had an overall positive effect on CPUE in all three years, regardless of plague status. Odds of capturing a unique animal were 1.10 (95% confidence interval [C.I.] 1.02–1.19) times higher per trap day on vaccine-treated plots than placebo plots in 2013, 1.47 (95% C.I. 1.41–1.52) times higher in 2014 and 1.19 (95% C.I. 1.13–1.25) times higher in 2015. On pairs where plague occurred, odds of apparent survival were 1.76 (95% Bayesian credible interval [B.C.I.] 1.28–2.43) times higher on vaccine plots than placebo plots for adults and 2.41 (95% B.C.I. 1.72–3.38) times higher for juveniles. Our results provide evidence that consumption of vaccine-laden baits can protect prairie dogs against plague; however, further evaluation and refinement are needed to optimize SPV use as a management tool.

Plague impacts prairie dogs ( Cynomys spp.), the endangered black-footed ferret ( Mustela nigripes ) and other sensitive wildlife species. We compared efficacy of prophylactic treatments (burrow dusting with deltamethrin or oral vaccination with recombinant “sylvatic plague vaccine” [RCN-F1/V307]) to placebo treatment in black-tailed prairie dog ( C. ludovicianus ) colonies. Between 2013 and 2015, we measured prairie dog apparent survival, burrow activity and flea abundance on triplicate plots (“blocks”) receiving dust, vaccine or placebo treatment. Epizootic plague affected all three blocks but emerged asynchronously. Dust plots had fewer fleas per burrow ( P  < 0.0001), and prairie dogs captured on dust plots had fewer fleas ( P  < 0.0001) than those on vaccine or placebo plots. Burrow activity and prairie dog density declined sharply in placebo plots when epizootic plague emerged. Patterns in corresponding dust and vaccine plots were less consistent and appeared strongly influenced by timing of treatment applications relative to plague emergence. Deltamethrin or oral vaccination enhanced apparent survival within two blocks. Applying insecticide or vaccine prior to epizootic emergence blunted effects of plague on prairie dog survival and abundance, thereby preventing colony collapse. Successful plague mitigation will likely entail strategic combined uses of burrow dusting and oral vaccination within large colonies or colony complexes.

Resistance and tolerance are two alternative strategies hosts can adopt to survive infections. Both strategies may be genetically controlled. To date, the relative contribution of resistance and tolerance to infection outcome is poorly understood. Here, we use a bioluminescent Listeria monocytogenes (Lm) infection challenge model to study the genetic determination and dynamic contributions of host resistance and tolerance to listeriosis in four genetically diverse mouse strains. Using conventional statistical analyses, we detect significant genetic variation in both resistance and tolerance, but cannot capture the time-dependent relative importance of either host strategy. We overcome these limitations through the development of novel statistical tools to analyse individual infection trajectories portraying simultaneous changes in infection severity and health. Based on these tools, early expression of resistance followed by expression of tolerance emerge as important hallmarks for surviving Lm infections. Our trajectory analysis further reveals that survivors and non-survivors follow distinct infection paths (which are also genetically determined) and provides new survival thresholds as objective endpoints in infection experiments. Future studies may use trajectories as novel traits for mapping and identifying genes that control infection dynamics and outcome. A Matlab script for user-friendly trajectory analysis is provided.

The use of dendritic cells (DCs) pulsed with defined Leishmania antigens could be a potential immune intervention tool for the induction of protection against infection. In the present study, bone marrow-derived DCs (BM-DCs) pulsed ex vivo with the peptide 12–31aa portion of kinetoplastid membrane protein (KMP)-11 (KMP-1112–31aa peptide) acquired a semimature phenotype expressing IL-12 and IL-10, whereas pulsing with the combination of the peptide and CpG oligodeoxynucleotides (ODNs) resulted in their functional maturation expressing mainly IL-12. Vaccination of genetically susceptible to parasite BALB/c mice with both peptide-pulsed BM-DCs elicited a peptide-specific mixed Th1/Th2 immune response, characterized by the production of IFNγ, IL-10 and IgG1 and IgG2a isotype antibodies. However, only BM-DCs pulsed with the combination of KMP-1112-31aa peptide and CpG ODNs induced the differentiation of peptide-specific Th17 cells, indicating the adjuvanticity of CpG ODNs. When BALB/c mice were vaccinated with KMP-1112–31aa peptide-pulsed BM-DCs, they exhibited only partial protection against Leishmania infantum challenge, whereas (KMP-1112–31aa peptide+CpG ODNs)-pulsed BM-DCs reduced efficiently the parasite load in visceral organs. Protective immunity was correlated with restoration of lymphoproliferative responses and a modulation of parasite-specific cellular responses towards Th1 and Th17 profile, confirmed by the isotype switching towards IgG2a, the enhanced production of IFNγ against IL-10, the absence of TGF-β and the overproduction of IL-17. Thus, ex vivo antigen-pulsed BM-DCs represent a powerful tool for the study of protective immune responses against leishmanial infection. Moreover, these findings suggest the use of BM-DCs as effective tools in antigen and adjuvant screening in the design of a protective vaccine against leishmaniasis and other pathogen-related infections.