RESUMEN
Spotted fever group rickettsiae (SFGR) are obligate intracellular bacteria that cause spotted fever. The limitations of gene manipulation pose great challenges to studying the infection mechanisms of Rickettsia. By combining bioorthogonal metabolism and click chemistry, we developed a method to label R. heilongjiangensis via azide moieties and achieved rapid pathogen localization without complex procedures. Moreover, we constructed a C57BL/6 mice infection model by simulating tick bites and discovered that the stomach is the target organ of R. heilongjiangensis infection through in vivo imaging systems, which explained the occurrence of gastrointestinal symptoms following R. heilongjiangensis infection in some cases. This study offers a unique perspective for subsequent investigations into the pathogenic mechanisms of SFGR and identifies a potential target organ for R. heilongjiangensis.
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Química Clic , Ratones Endogámicos C57BL , Rickettsia , Animales , Rickettsia/genética , Rickettsia/fisiología , Ratones , Química Clic/métodos , Estómago/microbiología , Modelos Animales de Enfermedad , Rickettsiosis Exantemáticas/microbiología , Femenino , Infecciones por Rickettsia/microbiología , Azidas/químicaRESUMEN
Rickettsia, a group of intracellular bacteria found in eukaryotes, exhibits diverse lifestyles, with some acting as vertebrate pathogens transmitted by arthropod vectors and others serving as maternally transmitted arthropod endosymbionts, some of which manipulate host reproduction for their own benefit. Two phenotypes, namely male-killing and parthenogenesis induction are known as Rickettsia-induced host reproductive manipulations, but it remains unknown whether Rickettsia can induce other types of host manipulation. In this study, we discovered that Rickettsia induced strong cytoplasmic incompatibility (CI), in which uninfected females produce no offspring when mated with infected males, in the predatory insect Nesidiocoris tenuis (Hemiptera: Miridae). Molecular phylogenetic analysis revealed that the Rickettsia strain was related to Rickettsia bellii, a common insect endosymbiont. Notably, this strain carried plasmid-encoded homologues of the CI-inducing factors (namely cifA-like and cifB-like genes), typically found in Wolbachia, which are well-known CI-inducing endosymbionts. Protein domain prediction revealed that the cifB-like gene encodes PD-(D/E)XK nuclease and deubiquitinase domains, which are responsible for Wolbachia-induced CI, as well as ovarian tumour-like (OTU-like) cysteine protease and ankyrin repeat domains. These findings suggest that Rickettsia and Wolbachia endosymbionts share underlying mechanisms of CI and that CI-inducing ability was acquired by microbes through horizontal plasmid transfer.
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Hemípteros , Filogenia , Rickettsia , Simbiosis , Animales , Rickettsia/fisiología , Femenino , Hemípteros/microbiología , Hemípteros/fisiología , Masculino , Citoplasma , Wolbachia/fisiologíaRESUMEN
Heritable symbionts are common among animals in nature, but the molecular mechanisms underpinning symbiont invasions of host populations have been elusive. In this study, we demonstrate the spread of Rickettsia in an invasive agricultural pest, the whitefly Bemisia tabaci Mediterranean (MED), across northeastern China from 2018 to 2023. Here, we show that the beneficial symbiont Rickettsia spreads by manipulating host hormone signals. Our analyses suggest that Rickettsia have been horizontally acquired by B. tabaci MED from another invasive whitefly B. tabaci Middle East-Asia Minor 1 during periods of coexistence. Rickettsia is transmitted maternally and horizontally from female B. tabaci MED individuals. Rickettsia infection enhances fecundity and results in female bias among whiteflies. Our findings reveal that Rickettsia infection stimulates juvenile hormone (JH) synthesis, in turn enhancing fecundity, copulation events, and the female ratio of the offspring. Consequently, Rickettsia infection results in increased whitefly fecundity and female bias by modulating the JH pathway. More female progeny facilitates the transmission of Rickettsia. This study illustrates that the spread of Rickettsia among invasive whiteflies in northeastern China is propelled by host hormone regulation. Such symbiont invasions lead to rapid physiological and molecular evolution in the host, influencing the biology and ecology of an invasive species.
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Fertilidad , Hemípteros , Rickettsia , Razón de Masculinidad , Simbiosis , Animales , Rickettsia/fisiología , Hemípteros/microbiología , Hemípteros/fisiología , Femenino , Masculino , Hormonas Juveniles/metabolismo , ChinaRESUMEN
Spotted fever group rickettsiae are tick-borne obligate intracellular bacteria that infect microvascular endothelial cells. Humans and mammalian infection results in endothelial cell barrier dysfunction and increased vascular permeability. We previously demonstrated that treatment of Rickettsia parkeri-infected cells with the calcium channel blocker benidipine significantly delayed vascular barrier permeability. Thus, we hypothesized that benidipine, known to be safe and effective for other clinical processes, could reduce rickettsia-induced vascular permeability in vivo in an animal model of spotted fever rickettsiosis. Based on liver, lung and brain vascular FITC-dextran extravasation studies, benidipine did not reliably impact vascular permeability. However, it precipitated a deleterious effect on responses to control sublethal R. parkeri infection. Animals treated with benidipine alone had no clinical signs or changes in histopathology and splenic immune cell distributions. Benidipine-treated infected animals had marked increases in tissue and blood bacterial loads, more extensive inflammatory histopathologic injury, and changes in splenic architecture and immune cell distributions potentially reflecting diminished Ca2+ signaling, reduced innate immune cell activation, and loss of rickettsial propagation control. Impaired T cell activation by R. parkeri antigen in the presence of benidipine was confirmed in vitro with the use of NKT cell hybridomas. The unexpected findings stand in stark contrast to recent discussions of the benefits of calcium channel blockers for viral infections and chronic infectious or inflammatory diseases. A role for calcium channel blockers in exacerbation of human rickettsiosis and acute inflammatory infections should be evaluated by a retrospective review of patient's outcomes and medications.
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Dihidropiridinas , Infecciones por Rickettsia , Rickettsia , Rickettsiosis Exantemáticas , Humanos , Ratones , Animales , Modelos Animales de Enfermedad , Bloqueadores de los Canales de Calcio , Células Endoteliales/patología , Infecciones por Rickettsia/microbiología , Rickettsia/fisiología , Rickettsiosis Exantemáticas/patología , Inmunidad Innata , MamíferosRESUMEN
IMPORTANCE: Pathogenic Rickettsia species are extremely dangerous bacteria that grow within the cytoplasm of host mammalian cells. In most cases, these bacteria are able to overpower the host cell and grow within the protected environment of the cytoplasm. However, a dramatic conflict occurs when Rickettsia encounter innate immune cells; the bacteria can "win" by taking over the host, or the bacteria can "lose" if the host cell efficiently fights the infection. This manuscript examines how the immune complement system is able to detect the presence of Rickettsia and alert nearby cells. Byproducts of complement activation called anaphylatoxins are signals that "activate" innate immune cells to mount an aggressive defensive strategy. This study enhances our collective understanding of the innate immune reaction to intracellular bacteria and will contribute to future efforts at controlling these dangerous infections.
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Rickettsia , Animales , Rickettsia/fisiología , Anafilatoxinas , Macrófagos , Proteínas del Sistema Complemento , Proliferación Celular , MamíferosRESUMEN
IMPORTANCE: Rickettsia spp. are intracellular bacterial parasites of a wide range of arthropod and vertebrate hosts. Some rickettsiae are responsible for several severe human diseases globally. One interesting feature of these pathogens is their ability to exploit host cytosolic defense responses to their benefits. However, the precise mechanism by which pathogenic Rickettsia spp. elude host defense responses remains unclear. Here, we observed that pathogenic Rickettsia typhi and Rickettsia rickettsii (Sheila Smith [SS]), but not non-pathogenic Rickettsia montanensis, become ubiquitinated and induce autophagy upon entry into macrophages. Moreover, unlike R. montanensis, R. typhi and R. rickettsii (SS) colocalized with LC3B but not with Lamp2 upon host cell entry. Finally, we observed that both R. typhi and R. rickettsii (SS), but not R. montanensis, reduce pro-inflammatory interleukin-1 (IL-1) responses, likely via an autophagy-mediated mechanism. In summary, we identified a previously unappreciated pathway by which both pathogenic R. typhi and R. rickettsii (SS) become ubiquitinated, induce autophagy, avoid autolysosomal destruction, and reduce microbicidal IL-1 cytokine responses to establish an intracytosolic niche in macrophages.
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Interleucina-1 , Rickettsia , Humanos , Citocinas , Rickettsia/fisiología , Macrófagos/microbiología , AutofagiaRESUMEN
Communities of bacteria, especially symbionts, are vital for the growth and development of insects and other arthropods, including Bemisia tabaci Mediterranean (MED), a destructive and invasive insect pest. However, the infection density patterns and influence factors of bacteria in whiteflies, which mainly include symbionts, remain largely unclear. To reveal the different density patterns of Cardinium in B. tabaci MED populations and the impacts of high temperatures on whiteflies with different Cardinium density infection patterns, 2 isofemale lines isolated from B. tabaci MED from the same geographical population of China and from B. tabaci MED collected from other countries and locations were examined using several techniques and methods, including fluorescence in situ hybridization (FISH), quantitative real-time polymerase chain reaction (qPCR), 16S rRNA gene sequencing, and 2b-RAD sequencing. The results showed that there were 2 different infection density patterns of Cardinium in B. tabaci MED (including 1 high-density pattern and 1 low-density pattern). For whiteflies with low-density Cardinium, conventional PCR could not detect Cardinium, but the other techniques confirmed that there was a low level of Cardinium within hosts. High temperature significantly decreased the diversity of bacterial communities: the relative titer of Cardinium increased but the density of Rickettsia decreased in the isofemale line with high-density Cardinium. However, high temperature did not influence the diversity and symbiont density in the line with low-density Cardinium. Moreover, high temperature influenced the functions of bacterial communities in whiteflies with high-density Cardinium but did not affect the bacterial functions in whiteflies with low-density Cardinium. Our results provide novel insights into the complex associations between symbionts and host insects.
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Hemípteros , Rickettsia , Animales , Hemípteros/genética , Calor , Hibridación Fluorescente in Situ , ARN Ribosómico 16S/genética , Simbiosis/genética , Bacteroidetes/genética , Insectos/genética , Rickettsia/fisiologíaRESUMEN
The guinea pig was the original animal model developed for investigating spotted fever rickettsiosis (SFR). This model system has persisted on account of the guinea pig's conduciveness to tick transmission of SFR agents and ability to recapitulate SFR in humans through clinical signs that include fever, unthriftiness, and in some cases the development of an eschar. The guinea pig is the smallest animal model for SFR that allows the collection of multiple blood and skin samples antemortem for longitudinal studies. This unit provides the basic protocols necessary to establish, maintain, and utilize a guinea pig-tick-Rickettsia model for monitoring the course of infection and immune response to an infection by spotted fever group Rickettsia (SFGR) that can be studied at biosafety level 2 (BSL-2) and arthropod containment level 2 (ACL-2); adaptations must be made for BSL-3 agents. The protocols cover methods for tick feeding and colony development, laboratory infection of ticks, tick transmission of Rickettsia to guinea pigs, and monitoring of the course of infection through clinical signs, rickettsial burden, and immune response. It should be feasible to adapt these methods to study other tick-borne pathogens. © 2022 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Tick transmission of SFGR to guinea pigs Support Protocol 1: Laboratory infection of ticks by injection Alternate Protocol 1: Needle inoculation of SFGR to guinea pigs Basic Protocol 2: Monitoring the course of guinea pig rickettsial infection: clinical signs Basic Protocol 3: Monitoring the course of guinea pig rickettsial infection: collection of biological specimens Support Protocol 2: Guinea pig anesthesia Basic Protocol 4: Monitoring rickettsial burden in guinea pigs by multiplex qPCR Basic Protocol 5: Monitoring guinea pig immune response to infection: blood leukocytes by flow cytometry Basic Protocol 6: Monitoring immune response to guinea pig rickettsial infection: leukocyte infiltration of skin at the tick bite site by flow cytometry Basic Protocol 7: Monitoring the immune response to guinea pig rickettsial infection: antibody titer by ELISA Support Protocol 4: Coating ELISA Plates Alternate Protocol 2: Monitoring immune response to guinea pig rickettsial infection: antibody titer by immunofluorescence assay.
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Rickettsiosis Exantemáticas , Garrapatas , Animales , Cobayas , Humanos , Modelos Animales de Enfermedad , Inmunidad , Infección de Laboratorio , Rickettsia/fisiología , Rickettsiosis Exantemáticas/diagnóstico , Rickettsiosis Exantemáticas/inmunología , Garrapatas/microbiologíaRESUMEN
The molecular details underlying differences in pathogenicity between Rickettsia species remain to be fully understood. Evidence points to macrophage permissiveness as a key mechanism in rickettsial virulence. Different studies have shown that several rickettsial species responsible for mild forms of rickettsioses can also escape macrophage-mediated killing mechanisms and establish a replicative niche within these cells. However, their manipulative capacity with respect to host cellular processes is far from being understood. A deeper understanding of the interplay between mildly pathogenic rickettsiae and macrophages and the commonalities and specificities of host responses to infection would illuminate differences in immune evasion mechanisms and pathogenicity. We used quantitative proteomics by sequential windowed data independent acquisition of the total high-resolution mass spectra with tandem mass spectrometry (SWATH-MS/MS) to profile alterations resulting from infection of THP-1 macrophages with three mildly pathogenic rickettsiae: Rickettsia parkeri, Rickettsia africae, and Rickettsia massiliae, all successfully proliferating in these cells. We show that all three species trigger different proteome signatures. Our results reveal a significant impact of infection on proteins categorized as type I interferon responses, which here included several components of the retinoic acid-inducible gene I (RIG-1)-like signaling pathway, mRNA splicing, and protein translation. Moreover, significant differences in protein content between infection conditions provide evidence for species-specific induced alterations. Indeed, we confirm distinct impacts on host inflammatory responses between species during infection, demonstrating that these species trigger different levels of beta interferon (IFN-ß), differences in the bioavailability of the proinflammatory cytokine interleukin 1ß (IL-1ß), and differences in triggering of pyroptotic events. This work reveals novel aspects and exciting nuances of macrophage-Rickettsia interactions, adding additional layers of complexity between Rickettsia and host cells' constant arms race for survival. IMPORTANCE The incidence of diseases caused by Rickettsia has been increasing over the years. It has long been known that rickettsioses comprise diseases with a continuous spectrum of severity. There are highly pathogenic species causing diseases that are life threatening if untreated, others causing mild forms of the disease, and a third group for which no pathogenicity to humans has been described. These marked differences likely reflect distinct capacities for manipulation of host cell processes, with macrophage permissiveness emerging as a key virulence trait. However, what defines pathogenicity attributes among rickettsial species is far from being resolved. We demonstrate that the mildly pathogenic Rickettsia parkeri, Rickettsia africae, and Rickettsia massiliae, all successfully proliferating in macrophages, trigger different proteome signatures in these cells and differentially impact critical components of innate immune responses by inducing different levels of beta interferon (IFN-ß) and interleukin 1ß (IL-1ß) and different timing of pyroptotic events during infection. Our work reveals novel nuances in rickettsia-macrophage interactions, offering new clues to understand Rickettsia pathogenicity.
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Inflamación , Macrófagos/microbiología , Proteínas/genética , Proteoma/genética , Infecciones por Rickettsia/inmunología , Rickettsia/inmunología , Humanos , Evasión Inmune , Macrófagos/inmunología , Proteínas/inmunología , Proteoma/inmunología , Rickettsia/clasificación , Rickettsia/genética , Rickettsia/fisiología , Infecciones por Rickettsia/genética , Infecciones por Rickettsia/microbiologíaRESUMEN
Horizontal gene transfer is widespread in insects bearing intracellular symbionts. Horizontally transferred genes (HTGs) are presumably involved in amino acid synthesis in sternorrhynchan insects. However, their role in insect-symbiont interactions remains largely unknown. We found symbionts Portiera, Hamiltonella and Rickettsia possess most genes involved in lysine synthesis in the whitefly Bemisia tabaci MEAM1 although their genomes are reduced. Hamiltonella maintains a nearly complete lysine synthesis pathway. In contrast, Portiera and Rickettsia require the complementation of whitefly HTGs for lysine synthesis and have lysE, encoding a lysine exporter. Furthermore, each horizontally transferred lysine gene of ten B. tabaci cryptic species shares an evolutionary origin. We demonstrated that Hamiltonella did not alter the titers of Portiera and Rickettsia or lysine gene expression of Portiera, Rickettsia and whiteflies. Hamiltonella also did not impact on lysine levels or protein localization in bacteriocytes harboring Portiera and ovaries infected with Rickettsia. Complementation with whitefly lysine synthesis HTGs rescued E. coli lysine gene knockout mutants. Silencing whitefly lysA in whiteflies harboring Hamiltonella reduced lysine levels, adult fecundity and titers of Portiera and Rickettsia without influencing the expression of Hamiltonella lysA. Furthermore, silencing whitefly lysA in whiteflies lacking Hamiltonella reduced lysine levels, adult fecundity and titers of Portiera and Rickettsia in ovarioles. Therefore, we, for the first time, demonstrated an essential amino acid lysine synthesized through HTGs is important for whitefly reproduction and fitness of both obligate and facultative symbionts, and it illustrates the mutual dependence between whitefly and its two symbionts. Collectively, this study reveals that acquisition of horizontally transferred lysine genes contributes to coadaptation and coevolution between B. tabaci and its symbionts.
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Evolución Molecular , Transferencia de Gen Horizontal , Halomonadaceae/fisiología , Hemípteros/microbiología , Lisina/metabolismo , Rickettsia/fisiología , Simbiosis , Animales , Hemípteros/genética , Hemípteros/crecimiento & desarrollo , Lisina/genéticaRESUMEN
Rickettsia is the pathogen of Q fever, Brucella ovis is the pathogen of brucellosis, and both of them are Gram-negative bacteria which are parasitic in cells. The mixed infection of rickettsia and Brucella ovis is rarely reported in clinic. Early diagnosis and treatment are of great significance to the treatment and prognosis of brucellosis and Q fever. Here, we report a case of co-infection Rickettsia burneti and Brucella melitensis. The patient is a 49-year-old sheepherder, who was hospitalized with left forearm trauma. Three days after admission, the patient developed fever of 39.0°C, accompanied by sweating, fatigue, poor appetite and headache. Indirect immunofluorescence (IFA) was used to detect Rickettsia burneti IgM. After 72 hours of blood culture incubation, bacterial growth was detected in aerobic bottles, Gram-negative bacilli were found in culture medium smear, the colony was identified as Brucella melitensis by mass spectrometry. Patients were treated with doxycycline (100 mg bid, po) and rifampicin (600 mg qd, po) for 4 weeks. After treatment, the symptoms disappeared quickly, and there was no sign of recurrence or chronic infection. Q fever and Brucella may exist in high-risk practitioners, so we should routinely detect these two pathogens to prevent missed diagnosis.
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Brucelosis/complicaciones , Brucelosis/diagnóstico , Coinfección , Infecciones por Rickettsia/complicaciones , Infecciones por Rickettsia/diagnóstico , Brucella melitensis/fisiología , Doxiciclina/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Rickettsia/fisiología , Rifampin/uso terapéutico , Resultado del TratamientoRESUMEN
Rickettsia africae is a bacterium of zoonotic importance, which causes African tick bite fever (ATBF) in humans. This pathogen is transmitted by ticks of the genus Amblyomma, with Amblyomma hebraeum and Amblyomma variegatum being the major vectors. Tick species other than the above-mentioned have also been reported to carry R. africae DNA. There is scarcity of information on the epidemiology of this pathogen, yet several cases have been recorded in foreign travellers who visited endemic areas, especially southern Africa. The disease has rarely been described in people from endemic regions. The aim of this study was to discuss the information that is currently available on the epidemiology of R. africae, highlighting the gaps in this field. Furthermore, ATBF cases, clinical signs and the locations where the cases occurred are also listed in this review.
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Interacciones Huésped-Patógeno , Infecciones por Rickettsia/epidemiología , Amblyomma , Animales , Femenino , Salud Global , Humanos , Masculino , Rickettsia/fisiología , Infecciones por Rickettsia/microbiología , Enfermedades por Picaduras de GarrapatasRESUMEN
Although Rickettsia species are molecularly detected among a wide range of arthropods, vector competence becomes an imperative aspect of understanding the ecoepidemiology of these vector-borne diseases. The synergy between vector homeostasis and rickettsial invasion, replication, and release initiated within hours (insects) and days (ticks) permits successful transmission of rickettsiae. Uncovering the molecular interplay between rickettsiae and their vectors necessitates examining the multifaceted nature of rickettsial virulence and vector infection tolerance. Here, we highlight the biological differences between tick- and insect-borne rickettsiae and the factors facilitating the incidence of rickettsioses. Untangling the complex relationship between rickettsial genetics, vector biology, and microbial interactions is crucial in understanding the intricate association between rickettsiae and their vectors.
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Vectores Artrópodos/microbiología , Interacciones Huésped-Patógeno/fisiología , Rickettsia/fisiología , Animales , Rickettsia/patogenicidadRESUMEN
Rickettsia parkeri rickettsiosis is recognized as the second most prevalent tick-borne disease caused by spotted fever group rickettsiae in the Americas, where two pathogenic strains (R. parkeri sensu stricto and R. parkeri strain Atlantic rainforest) have been related to human infections and transmitted by Amblyomma spp. ticks. We developed a systematic review that evaluated all available evidence in the literature regarding clinical, epidemiological, and laboratory features of R. parkeri rickettsiosis, including confirmed and probable cases. We followed the recommendations made by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guide. We excluded papers that contained missing information of some variables and publications in which it was not possible to separate data for confirmed and probable cases. A total of 77 clinical cases (32 confirmed cases and 45 probable cases) were considered for this review. Overall, our results show that R. parkeri rickettsiosis is more frequent in males in the age group of 18-64 years and that a history of tick exposure was frequent (>90%). Cases were described in the United States, Argentina, Brazil, Uruguay and Colombia. Clinically, more than 60% of the cases had fever (mean of 93%), eschar (mean of 87%), and rash (mean of 68%). Headache and myalgia were predominant nonspecific symptoms (mean of 67% and 61%, respectively). Our results show that at least 60% of R. parkeri cases had altered laboratory parameters, most often showing an increase in transaminases and leukopenia. Tetracyclines-class antibiotics were used in most (>85%) of the patients. Overall, only 9% of cases required hospitalization and there was a 100% rate of clinical recovery in all of cases.
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Infecciones por Rickettsia , Rickettsia/fisiología , Humanos , Infecciones por Rickettsia/epidemiología , Infecciones por Rickettsia/microbiologíaRESUMEN
Biological interactions can greatly influence the abundance of species. This is also true for parasitic species that share the same host. Microsporidia and Rickettsia are widespread intracellular parasites in populations of Paracalliope fluviatilis, the most common freshwater amphipods in New Zealand. Although both parasites coexist in many populations, it is unclear whether they interact with each other. Here, we investigated spatial−temporal dynamics and co-occurrence of the two parasites, Microsporidia and Rickettsia in P. fluviatilis hosts, across one annual cycle and in three different locations. Prevalence of both Microsporidia and Rickettsia changed over time. However, while the prevalence of Rickettsia varied significantly between sampling times, that of Microsporidia did not change significantly and remained relatively low. The two parasites therefore followed different temporal patterns. Also, the prevalence of both parasites differed among locations, though the two species reached their highest prevalence in different locations. Lastly, there was no evidence for positive or negative associations between the two parasite species; the presence of one parasite in an individual host does not appear to influence the probability of infection by the other parasite. Their respective prevalence may follow different patterns among populations on a larger spatial scale due to environmental heterogeneity across locations.
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Anfípodos/parasitología , Interacciones Huésped-Parásitos , Microsporidios/aislamiento & purificación , Rickettsia/aislamiento & purificación , Animales , Microsporidios/fisiología , Nueva Zelanda , Rickettsia/fisiología , Análisis Espacio-TemporalRESUMEN
We recently reported that the in vitro and in vivo survivals of Rickettsia australis are Atg5-dependent, in association with an inhibited level of anti-rickettsial cytokine, IL-1ß. In the present study, we sought to investigate how R. australis interacts with host innate immunity via an Atg5-dependent autophagic response. We found that the serum levels of IFN-γ and G-CSF in R. australis-infected Atg5flox/flox Lyz-Cre mice were significantly less compared to Atg5flox/flox mice, accompanied by significantly lower rickettsial loads in tissues with inflammatory cellular infiltrations including neutrophils. R. australis infection differentially regulated a significant number of genes in bone marrow-derived macrophages (BMMs) in an Atg5-depdent fashion as determined by RNA sequencing and Ingenuity Pathway Analysis, including genes in the molecular networks of IL-1 family cytokines and PI3K-Akt-mTOR. The secretion levels of inflammatory cytokines, such as IL-1α, IL-18, TNF-α, and IL-6, by R. australis-infected Atg5flox/flox Lyz-Cre BMMs were significantly greater compared to infected Atg5flox/flox BMMs. Interestingly, R. australis significantly increased the levels of phosphorylated mTOR and P70S6K at a time when the autophagic response is induced. Rapamycin treatment nearly abolished the phosphorylated mTOR and P70S6K but did not promote significant autophagic flux during R. australis infection. These results highlight that R. australis modulates an Atg5-dependent autophagic response, which is not sensitive to regulation by mTORC1 signaling in macrophages. Overall, we demonstrate that R. australis counteracts host innate immunity including IL-1ß-dependent inflammatory response to support the bacterial survival via an mTORC1-resistant autophagic response in macrophages.
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Proteína 5 Relacionada con la Autofagia/metabolismo , Macrófagos/inmunología , Infecciones por Rickettsia/inmunología , Rickettsia/fisiología , Animales , Autofagia/genética , Proteína 5 Relacionada con la Autofagia/genética , Citocinas/metabolismo , Redes Reguladoras de Genes , Humanos , Inmunidad Innata , Mediadores de Inflamación/metabolismo , Ratones , Ratones Endogámicos C57BL , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
Ticks are haematophagous arthropods with unique molecular mechanisms for digesting host blood meal while acting as vectors for various pathogens of public health significance. The tick's pharmacologically active saliva plays a fundamental role in modulating the host's immune system for several days to weeks, depending on the tick species. The vector tick has also developed sophisticated molecular mechanisms to serve as a competent vector for pathogens, including the spotted fever group (SFG) rickettsiae. Evidence is still inadequate concerning tick-rickettsiae-host interactions and saliva-assisted transmission of the pathogen to the mammalian host. Rickettsia parkeri, of the SFG rickettsia, can cause a milder version of Rocky Mountain spotted fever known as American Boutonneuse fever. The Gulf Coast tick (Amblyomma maculatum) often transmits this pathogenic rickettsia in the USA. This review discusses the knowledge gap concerning tick-rickettsiae-host interactions by highlighting the SFG rickettsia and the Am maculatum model system. Filling this knowledge gap will provide a better understanding of the tick-rickettsiae-host interactions in disease causation, which will be crucial for developing effective methods for preventing tick-borne diseases.
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Antioxidantes/fisiología , Infecciones por Rickettsia/microbiología , Rickettsia/fisiología , Garrapatas/microbiología , Garrapatas/fisiología , Animales , Modelos Animales de Enfermedad , Ixodidae/microbiología , Ixodidae/fisiología , Microbiota , Oxidación-Reducción , Rickettsia/clasificación , Infecciones por Rickettsia/transmisión , Saliva/microbiología , Selenoproteínas/genética , Selenoproteínas/metabolismo , SimbiosisRESUMEN
OBJECTIVE: This study aimed to describe the epidemiological and clinical characteristics of endemics of two rickettsial diseases, scrub typhus (ST) and Japanese spotted fever (JSF), in Japan. METHODS: We conducted a retrospective, descriptive epidemiological assessment of cases notified via national surveillance from 2007-2016. RESULTS: Over the 10-year period, 4185 ST and 1765 JSF cases were notified; of these, 20 (0.48%) cases of ST and 16 (0.91%) cases of JSF were fatal at the time of reporting. The elderly had higher notification rates and fatalities. While the annual number of ST notifications was stable and cases were reported from a broad geographic range, the number of JSF reports increased three-fold, expanding from the southwest to the east. The seasonality of ST varied by region and was more common during spring/summer in the north and autumn/winter in the south; 78% of cases occurred during autumn/winter, mainly in the southern region. Most of the fatal ST cases occurred in the spring/summer and occurred in the northern region. CONCLUSION: Our analysis identified seasonal and regional variations in the distribution of rickettsiosis. These variations were most likely to be related to the ecology of the vectors and etiological agents. Knowing the recent epidemiological and clinical features of ST and JSF can support clinical diagnosis and guide preventative activities against these vector-borne diseases.
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Infecciones por Rickettsia/epidemiología , Rickettsia/fisiología , Tifus por Ácaros/epidemiología , Rickettsiosis Exantemáticas/epidemiología , Enfermedades Transmitidas por Vectores/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Enfermedades Endémicas , Femenino , Humanos , Lactante , Japón/epidemiología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Infecciones por Rickettsia/microbiología , Tifus por Ácaros/microbiología , Estaciones del Año , Rickettsiosis Exantemáticas/microbiología , Enfermedades Transmitidas por Vectores/microbiología , Adulto JovenRESUMEN
The genus Rickettsia encompasses 35 valid species of intracellular, coccobacilli bacteria that can infect several eukaryotic taxa, causing multiple emerging and re-emerging diseases worldwide. This work aimed to gather and summarise the current knowledge about the genus Rickettsia in Mexico, updating the taxonomy of the bacteria and their hosts by including all the records available until 2020, to elucidate host-parasite relationships and determine the geographical distribution of each Rickettsia species present in the country. Until now, 14 species of Rickettsia belonging to four groups have been recorded in Mexico. These species have been associated with 26 arthropod species (14 hard ticks, three soft ticks, two sucking lice, and seven fleas) and 17 mammal species distributed over 30 states in Mexico. This work highlights the high biological inventory of rickettsias for Mexico and reinforces the need to approach the study of this group from a One Health perspective.
Asunto(s)
Anoplura/microbiología , Interacciones Huésped-Patógeno , Mamíferos/microbiología , Rickettsia/fisiología , Siphonaptera/microbiología , Garrapatas/microbiología , Animales , Interacciones Huésped-Parásitos , MéxicoRESUMEN
This cross-sectional study explores the different conditions related to the infestation of ticks in households and the potential risks for rickettsial transmission in Urabá, Colombia. The main outcome of interest was villagers' perception of tick infestation. The data were analyzed using a clog-log mixed regression model. Ticks were collected from infested humans to diagnose infection by spotted fever group rickettsiae (SFGR). In addition, a thematic analysis of qualitative data from key informants concerning knowledge about ticks was conducted. The prevalence of infestation of ticks in households was estimated at 60.99% (95% CI: 51.58-93.51). The multivariate model suggested that households with palm leaf roofs (PR = 1.95; 95% CI: 1.19-2.95), canines (PR = 1.76; 95% CI: 1.21-2.46), rats (PR = 2.19; 95% CI: 1.45-3.08), and with the presence of opossums in areas surrounding the households (PR = 1.51; 95% CI: 1.05-2.10) had a higher prevalence of tick infestation. Two samples of the tick species Amblyomma patinoi were found infected with Rickettsia amblyommatis and Candidatus Rickettsia colombianensi. A thematic analysis provided the names that local community members give to ticks, areas where ticks are common, and the individuals at risk of infestation. The presence of domestic, synanthropic, and wild animals suggests a high risk of the dissemination of ticks inside dwellings and close to them in these rural areas.