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An infection with the tick-borne Rickettsia helvetica has been associated with a broad spectrum of clinical manifestations in humans, but patients are only seldomly reported. Understanding its disease etiology necessitates well-stablished infection models, improving to recognize and diagnose patients with R. helvetica infection and facilitating the development of effective control strategies. In this study, we used C3H/HeN mice as a model to establish R. helvetica infection, achieving a high infection prevalence (89–100 %). While the liver and the spleen DNA consistently tested positive for infection in all challenged mice, additional infected organs included the kidneys, heart, and the lungs. Notably, a low prevalence of infection was observed in I. ricinus nymphs fed on R. helvetica-challenged mice. In addition, larvae were refractory to infection, suggesting that ticks exhibit low susceptibility to the pathogen. To the best of our knowledge, this is the first study of an animal model for R. helvetica infection. It serves as a valuable tool for advancing research on the interactions among the bacterium and its vertebrate host.

Abstract Background Ticks can transmit a broad variety of pathogens of medical importance, including Borrelia afzelii, the causative agent of Lyme borreliosis in Europe. Tick microbiota is an important factor modulating, not only vector physiology, but also the vector competence. Anti-microbiota vaccines targeting keystone taxa of tick microbiota can alter tick feeding and modulate the taxonomic and functional profiles of bacterial communities in the vector. However, the impact of anti-microbiota vaccine on tick-borne pathogen development within the vector has not been tested. Results Here, we characterized the Ixodes ricinus microbiota modulation in response to B. afzelii infection and found that the pathogen induces changes in the microbiota composition, its beta diversity and structure of bacterial community assembly. Tick microbiota perturbation by anti-microbiota antibodies or addition of novel commensal bacteria into tick midguts causes departures from the B. afzelii-induced modulation of tick microbiota which resulted in a lower load of the pathogen in I. ricinus. Co-occurrence networks allowed the identification of emergent properties of the bacterial communities which better defined the Borrelia infection-refractory states of the tick microbiota. Conclusions These findings suggest that Borrelia is highly sensitive to tick microbiota perturbations and that departure from the modulation induced by the pathogen in the vector microbiota pose a high cost to the spirochete. Network analysis emerges as a suitable tool to identify emergent properties of the vector microbiota associated with infection-refractory states. Anti-microbiota vaccines can be used as a tool for microbiota perturbation and control of important vector-borne pathogens. Video Abstract

Abstract Background Ticks and tick-borne pathogens significantly impact both human and animal health and therefore are of major concern to the scientific community. Knowledge of tick-borne pathogens is crucial for prescription of mitigation measures. In Africa, much research on ticks has focused on domestic animals. Little is known about ticks and their pathogens in wild habitats and wild animals like the endangered chimpanzee, our closest relative. Methods In this study, we collected ticks in the forested habitat of a community of 100 chimpanzees living in Kibale National Park, Western Uganda, and assessed how their presence and abundance are influenced by environmental factors. We used non-invasive methods of flagging the vegetation and visual search of ticks both on human team members and in chimpanzee nests. We identified adult and nymph ticks through morphological features. Molecular techniques were used to detect and identify tick-borne piroplasmids and bacterial pathogens. Results A total of 470 ticks were collected, which led to the identification of seven tick species: Haemaphysalis parmata (68.77%), Amblyomma tholloni (20.70%), Ixodes rasus sensu lato (7.37%), Rhipicephalus dux (1.40%), Haemaphysalis punctaleachi (0.70%), Ixodes muniensis (0.70%) and Amblyomma paulopunctatum (0.35%). The presence of ticks, irrespective of species, was influenced by temperature and type of vegetation but not by relative humidity. Molecular detection revealed the presence of at least six genera of tick-borne pathogens (Babesia, Theileria, Borrelia, Cryptoplasma, Ehrlichia and Rickettsia). The Afrotopical tick Amblyomma tholloni found in one chimpanzee nest was infected by Rickettsia sp. Conclusions In conclusion, this study presented ticks and tick-borne pathogens in a Ugandan wildlife habitat whose potential effects on animal health remain to be elucidated. Graphical Abstract

Abstract Up to 170 tick-borne viruses (TBVs) have been identified to date. However, there is a paucity of information regarding TBVs and their interaction with respective vectors, limiting the development of new effective and urgently needed control methods. To overcome this gap of knowledge, it is essential to reproduce transmission cycles under controlled laboratory conditions. In this study we assessed an artificial feeding system (AFS) and an immersion technique (IT) to infect Ixodes ricinus ticks with tick-borne encephalitis (TBE) and Kemerovo (KEM) virus, both known to be transmitted predominantly by ixodid ticks. Both methods permitted TBEV acquisition by ticks and we further confirmed virus trans-stadial transmission and onward transmission to a vertebrate host. However, only artificial feeding system allowed to demonstrate both acquisition by ticks and trans-stadial transmission for KEMV. Yet we did not observe transmission of KEMV to mice (IFNAR−/− or BALB/c). Artificial infection methods of ticks are important tools to study tick-virus interactions. When optimally used under laboratory settings, they provide important insights into tick-borne virus transmission cycles.

Abstract Herein, we report the first identification of biallelic‐inherited mutations in ALPI as a Mendelian cause of inflammatory bowel disease in two unrelated patients. ALPI encodes for intestinal phosphatase alkaline, a brush border metalloenzyme that hydrolyses phosphate from the lipid A moiety of lipopolysaccharides and thereby drastically reduces Toll‐like receptor 4 agonist activity. Prediction tools and structural modelling indicate that all mutations affect critical residues or inter‐subunit interactions, and heterologous expression in HEK293T cells demonstrated that all ALPI mutations were loss of function. ALPI mutations impaired either stability or catalytic activity of ALPI and rendered it unable to detoxify lipopolysaccharide‐dependent signalling. Furthermore, ALPI expression was reduced in patients’ biopsies, and ALPI activity was undetectable in ALPI‐deficient patient's stool. Our findings highlight the crucial role of ALPI in regulating host–microbiota interactions and restraining host inflammatory responses. These results indicate that ALPI mutations should be included in screening for monogenic causes of inflammatory bowel diseases and lay the groundwork for ALPI‐based treatments in intestinal inflammatory disorders.

PrPC protein plays a key role in prion transmission across species. Here, the authors compare transmission of a representative scrapie isolate to transgenic mice expressing variable levels of the same Prnp allele as the donor sheep, and find divergent strain propagation regulated by PrPCgene dosage.

Synthetic peptide vaccines were designed to target the neuropeptides innervating Ixodes ricinus salivary glands and hindgut and they were tested for their capacity to afford protective immunity against nymphs or larvae and Anaplasma phagocytophilum-infected nymph infestation, in mice and sheep, respectively. In both models, the assembly of SIFamide (SIFa) or myoinhibitory peptide (MIP) neuropeptides into multiple antigenic peptide constructs (MAPs) elicited a robust IgG antibody response following immunization. Nevertheless, no observable detrimental impact on nymphs was evidenced in mice, and, unfortunately, the number of engorged nymphs on sheep was insufficient for firm conclusions to be drawn, including for bacterial transmission. Regarding larvae, while vaccination of the sheep did not globally diminish tick feeding success or development, analyses of animals at the individual level revealed a negative correlation between anti-SIFa and MIP antibody levels and larva-to-nymph molting success for both antigens. Our results provide a proof of principle and precedent for the use of MAPs for the induction of immunity against tick peptide molecules. Although the present study did not provide the expected level of protection, it inaugurates a new strategy for protection against ticks based on the immunological targeting of key components of their nervous system.

To identify potential vaccine candidates against Ixodes ricinus and tick-borne pathogen transmission, we have previously sequenced the salivary gland transcriptomes of female ticks infected or not with Bartonella henselae. The hypothesized potential of both IrSPI (I. ricinus serine protease inhibitor) and IrLip1 (I. ricinus lipocalin 1) as protective antigens decreasing tick feeding and/or the transmission of tick-borne pathogens was based on their presumed involvement in dampening the host immune response to tick feeding. Vaccine endpoints included tick larval and nymphal mortality, feeding, and molting in mice and sheep. Whether the antigens were administered individually or in combination, the vaccination of mice or sheep elicited a potent antigen-specific antibody response. However, and contrary to our expectations, vaccination failed to afford protection against the infestation of mice and sheep by I. ricinus nymphs and larvae, respectively. Rather, vaccination with IrSPI and IrLip1 appeared to enhance tick engorgement and molting and decrease tick mortality. To the best of our knowledge, these observations represent the first report of induction of vaccine-mediated enhancement in relation to anti-tick vaccination.

Naturally occurring human antibodies (Abs) of the isotypes IgM and IgG and reactive to the galactose-α-1,3-galactose (α-Gal) epitope are associated with protection against infectious diseases, caused by pathogens expressing the glycan. Gut microbiota bacteria expressing α-Gal regulate the immune response to this glycan in animals lacking endogenous α-Gal. Here, we asked whether the production of anti-α-Gal Abs in response to microbiota stimulation in birds, confers protection against infection by Aspergillus fumigatus, a major fungal pathogen that expresses α-Gal in its surface. We demonstrated that the oral administration of Escherichia coli O86:B7 strain, a bacterium with high α-Gal content, reduces the occurrence of granulomas in lungs and protects turkeys from developing acute aspergillosis. Surprisingly, the protective effect of E. coli O86:B7 was not associated with an increase in circulating anti-α-Gal IgY levels, but with a striking reduction of anti-α-Gal IgA in the lungs of infected turkeys. Subcutaneous immunization against α-Gal did not induce a significant reduction of lung anti-α-Gal IgA and failed to protect against an infectious challenge with A. fumigatus. Oral administration of E. coli O86:B7 was not associated with the upregulation of lung cytokines upon A. fumigatus infection. We concluded that the oral administration of bacteria expressing high levels of α-Gal decreases the levels of lung anti-α-Gal IgA, which are mediators of inflammation and lung damage during acute aspergillosis.

Bacterial diversification is often observed, but underlying mechanisms are difficult to disentangle and remain generally unknown. Moreover, controlled diversification experiments in ecologically relevant environments are lacking. We studied bacterial diversification in the mammalian gut, one of the most complex bacterial environments, where usually hundreds of species and thousands of bacterial strains stably coexist. Herein we show rapid genetic diversification of an Escherichia coli strain upon colonisation of previously germ-free mice. In addition to the previously described mutations in the EnvZ/OmpR operon, we describe the rapid and systematic selection of mutations in the flagellar flhDC operon and in malT, the transcriptional activator of the maltose regulon. Moreover, within each mouse, the three mutant types coexisted at different levels after one month of colonisation. By combining in vivo studies and determination of the fitness advantages of the selected mutations in controlled in vitro experiments, we provide evidence that the selective forces that drive E. coli diversification in the mouse gut are the presence of bile salts and competition for nutrients. Altogether our results indicate that a trade-off between stress resistance and nutritional competence generates sympatric diversification of the gut microbiota. These results illustrate how experimental evolution in natural environments enables identification of both the selective pressures that organisms face in their natural environment and the diversification mechanisms.

While pleiotropic adaptive mutations are thought to be central for evolution, little is known on the downstream molecular effects allowing adaptation to complex ecologically relevant environments. Here we show that Escherichia coli MG1655 adapts rapidly to the intestine of germ-free mice by single point mutations in EnvZ/OmpR two-component signal transduction system, which controls more than 100 genes. The selective advantage conferred by the mutations that modulate EnvZ/OmpR activities was the result of their independent and additive effects on flagellin expression and permeability. These results obtained in vivo thus suggest that global regulators may have evolved to coordinate activities that need to be fine-tuned simultaneously during adaptation to complex environments and that mutations in such regulators permit adjustment of the boundaries of physiological adaptation when switching between two very distinct environments.