Detection of Anaplasma and Ehrlichia bacteria in humans, wildlife, and ticks in the Amazon rainforest.

Tick-borne bacteria of the genera Ehrlichia and Anaplasma cause several emerging human infectious diseases worldwide. In this study, we conduct an extensive survey for Ehrlichia and Anaplasma infections in the rainforests of the Amazon biome of French Guiana. Through molecular genetics and metagenomics reconstruction, we observe a high indigenous biodiversity of infections circulating among humans, wildlife, and ticks inhabiting these ecosystems. Molecular typing identifies these infections as highly endemic, with a majority of new strains and putative species specific to French Guiana. They are detected in unusual rainforest wild animals, suggesting they have distinctive sylvatic transmission cycles. They also present potential health hazards, as revealed by the detection of Candidatus Anaplasma sparouinense in human red blood cells and that of a new close relative of the human pathogen Ehrlichia ewingii, Candidatus Ehrlichia cajennense, in the tick species that most frequently bite humans in South America. The genome assembly of three new putative species obtained from human, sloth, and tick metagenomes further reveals the presence of major homologs of Ehrlichia and Anaplasma virulence factors. These observations converge to classify health hazards associated with Ehrlichia and Anaplasma infections in the Amazon biome as distinct from those in the Northern Hemisphere.

Molecular diagnosis and characterization of Anaplasma marginale and Ehrlichia ruminantium infecting beef cattle of Maputo Province, Mozambique.

BACKGROUND: Members of the Anaplasmataceae family, such as the Anaplasma and Ehrlichia species, cause economic losses and public health risks. However, the exact economic impact has not been comprehensively assessed in Mozambique due to limited data available on its basic epidemiology. Therefore, we investigated the molecular occurrence and identity of Anaplasma and Ehrlichia spp. infecting beef cattle in Maputo province, Mozambique. METHODS: A total of 200 whole blood samples were collected from apparently healthy beef cattle. Whole blood DNA was extracted and tested for presence of Anaplasma spp. and Ehrlichia ruminantium DNA through amplification of the 16S rRNA and map1 genes. Positive samples to Anaplasma spp. were subject to PCR assay targeting the A. marginale-msp5 gene. Amplicons obtained were purified, sequenced and subject to phylogenetic analyses. RESULTS: Anaplasma spp., A. marginale and E. ruminantium were detected in 153 (76.5%), 142 (71%) and 19 (9.5%) of all the samples analyzed, respectively. On this same sample group, 19 (9.5%) were co-infected with A. marginale and E. ruminantium. The 16S rRNA sequences of Anaplasma spp. obtained were phylogenetically related to A. marginale, A. centrale and A. platys. Phylogenetic analysis revealed that A. marginale-msp5 nucleotide sequences were grouped with sequences from Asia, Africa and Latin America, whereas E. ruminantium-map1 DNA nucleotide sequences were positioned in multiple clusters. CONCLUSION: Cattle in Maputo Province are reservoirs for multiple Anaplasma species. A high positivity rate of infection by A. marginale was observed, as well as high genetic diversity of E. ruminantium. Furthermore, five new genotypes of E. ruminantium-map1 were identified.

Dog blood parasite infection in upland and lowland communities of northern Thailand: The role of environment and care of dog owners.

Dogs play an important role as hosts and reservoirs for many zoonotic diseases. Ehrlichiosis, babesiosis and hepatozoonosis are a group of canine vector-borne diseases that can be transmitted via ectoparasites from dog to dog and also from dog to humans. This study focused on three main blood parasites of dog (i.e., Babesia spp., Ehrlichia spp. and Hepatozoon spp.) among two different landscape types of eight villages of Santhong Sub-district, Nan Province, Thailand. In this study, 149 dogs were surveyed and blood samples were collected. Blood parasite infections in dogs were assessed using molecular detection approach. Babesia canis vogeli, Babesia gibsoni, Ehrlichia canis and Hepatozoon canis were detected with prevalence of infection at 10.7%, 8.1%, 3.4% and 0.7%, respectively. In terms of landscape type, prevalence of overall blood parasites, particularly Babesia spp. infections were higher in dogs living in upland forested areas (28.3%) compared to dogs from lowland agricultural areas (12.3%). Data obtained from the questionnaires on perceptions of dog owners showed that dogs raised all the time outside owner's house, and those dogs whose owners have never bathed and cleaned were more likely to be exposed to blood parasites. As infected dogs could play an important role as reservoirs of the blood parasites, attitude of dog owners may affect public health in terms of zoonotic disease transmission. Effective control measures and surveillance program of arthropod vectors and blood parasite infection in dogs still need to be advocated to minimize zoonotic disease transmission.

Anaplasma phagocytophilum in urban and peri-urban passerine birds in Ile-de-France.

Wild animals in general, birds in particular, play a key role in transporting ticks and propagating tick-borne pathogens. Several studies have confirmed the infection of birds with Anaplasma phagocytophilum, with overall prevalence varying widely from country to country and/or study to study. This zoonotic bacterium, transmitted mainly by ticks of the genus Ixodes, is responsible for granulocytic anaplasmosis in humans (HGA) and domestic animals (cats, dogs, horses). The disease is also called tick-borne fever (TBF) in ruminants. Extremely rare in the USA, TBF is very common in Europe, where it causes economic losses in livestock. Conversely, HGA is well established in the USA whereas only a few less severe cases have been observed in Europe. Current typing techniques support the existence of multiple variants with differences in virulence/pathogenicity and tropism for certain tick and host species. However, epidemiological cycles remain difficult to characterize in Europe. Several studies describe a cycle apparently involving only birds in Europe, but no such study has been conducted in mainland France. Our objectives were to search for A. phagocytophilum in passerine birds in the Ile-de-France region and to explore their diversity using groEL and ankA gene typing and multilocus sequence typing (MLST). Various tissues (spleen, liver, and skin) were collected from cadavers of 680 passerines between March and December 2021. The presence of A. phagocytophilum was detected by qPCR Taqman targeting the msp2 gene. Three blackbirds (Turdus merula) were found positive, representing detection rates of 0.4 % in all birds tested and 3.3 % in blackbirds. The higher frequency of detection in blackbirds could be at least partially explained by their lifestyle, as they feed on the ground. Analysis of the results of groEL and ankA typing and MLST from positive blackbirds support the hypothesis that the avian A. phagocytophilum strains in Ile-de-France are distinct from those found in mammals, and that they form their own cluster in Europe.

Assessment of the effect of long-term serum storage for retrospective serologic diagnosis of canine monocytic ehrlichiosis (Ehrlichia canis).

There is currently sparse information on the possible effect of long-term storage of serum specimens for the retrospective serodiagnosis of canine monocytic ehrlichiosis (CME). The aim of this study was to assess the agreement between the original serologic outcome and the results of a repeat indirect fluorescent antibody (IFA) assay for the detection of IgG antibodies against E. canis. A secondary aim was to compare the diagnostic performance of two commercially available point-of-care (POC) immunochromatographic (IC) assays. Archived serum samples originally tested as positive (n=66) or negative (n=19) for E. canis IgG antibodies and kept frozen at -20°C for a median of 22 years, were retrospectively examined by IFA and by two POC IC assays. Cohen's Kappa coefficient (0.748, p < 0.0001), indicated a substantial agreement between the original and repeat serologic testing results. An almost identical high sensitivity and moderate specificity were established for the two POC IC assays. Canine serum specimens on long-term storage may still be of value for seroepidemiologic surveys investigating the exposure to E. canis.

Tick-Borne Diseases.

Ticks are responsible for the vast majority of vector-borne illnesses in the United States. The number of reported tick-borne disease (TBD) cases has more than doubled in the past 20 years. The majority of TBD cases occur in warm weather months in individuals with recent outdoor activities in wooded areas. The risk of contracting a TBD is also highly dependent on geographic location. Between 24 and 48 hours of tick attachment is required for most disease transmission to occur. Only 50% to 70% of patients with a TBD will recall being bitten by a tick, and TBDs are often initially misdiagnosed as a viral illness. Most TBDs are easily treated when diagnosed early in their course.

What's Eating You? Rhipicephalus Ticks Revisited.

Rhipicephalus ticks are vectors of disease in humans and animals. Rhipicephalus sanguineus sensu lato (the brown dog tick) is one of the most geographically widespread tick species worldwide, likely due to its ability to colonize human and canine dwellings over a range of habitats. They transmit a variety of diseases to dogs and humans, including canine babesiosis, canine monocytic ehrlichiosis, hepatozoonosis, Mediterranean spotted fever, and Rocky Mountain spotted fever. Tick bites manifest as intensely pruritic, erythematous papules at the site of tick attachment; symptomatic relief usually can be achieved with topical antipruritics. Prevention of tick bites is best achieved through a combination of veterinary and environmental control; protective clothing; repellents, such as N,N-diethyl-meta-toluamide (DEET) and permethrin; and prompt identification and removal of ticks.

Ehrlichia effector TRP120 manipulates bacteremia to facilitate tick acquisition.

Ehrlichia species are obligatory intracellular bacteria that cause a potentially fatal disease, human ehrlichiosis. The biomolecular mechanisms of tick acquisition of Ehrlichia and transmission between ticks and mammals are poorly understood. Ehrlichia japonica infection of mice recapitulates the full spectrum of human ehrlichiosis. We compared the pathogenicity and host acquisition of wild-type E. japonica with an isogenic transposon mutant of E. japonica that lacks tandem repeat protein 120 (TRP120) (ΔTRP120). Both wild-type and ΔTRP120 E. japonica proliferated similarly in cultures of mammalian and tick cells. Upon inoculation into mice, both wild-type and ΔTRP120 E. japonica multiplied to high levels in various tissues, with similar clinical chemistry and hematologic changes, proinflammatory cytokine induction, and fatal disease. However, the blood levels of ΔTRP120 E. japonica were almost undetectable within 24 h, whereas the levels of the wild type increased exponentially. Greater than 90% of TRP120 was released from infected cells into the culture medium. Mouse blood monocytes exposed to native TRP120 from culture supernatants showed significantly reduced cell surface expression of the transmigration-related markers Ly6C and CD11b. Larval ticks attached to mice infected with either wild-type or ΔTRP120 E. japonica imbibed similar amounts of blood and subsequently molted to nymphs at similar rates. However, unlike wild-type E. japonica, the ΔTRP120 mutant was minimally acquired by larval ticks and subsequent molted nymphs and, thus, failed to transmit to naïve mice. Thus, TRP120 is required for bacteremia but not disease. These findings suggest a novel mechanism whereby an obligatory intracellular bacterium manipulates infected blood monocytes to sustain the tick-mammal transmission cycle. IMPORTANCE: Effective prevention of tick-borne diseases such as human ehrlichiosis requires an understanding of how disease-causing organisms are acquired. Ehrlichia species are intracellular bacteria that require infection of both mammals and ticks, involving cycles of transmission between them. Mouse models of ehrlichiosis and tick-mouse transmission can advance our fundamental understanding of the pathogenesis and prevention of ehrlichiosis. Herein, a mutant of Ehrlichia japonica was used to investigate the role of a single Ehrlichia factor, named tandem repeat protein 120 (TRP120), in infection of mammalian and tick cells in culture, infection and disease progression in mice, and tick acquisition of E. japonica from infected mice. Our results suggest that TRP120 is necessary only for Ehrlichia proliferation in circulating mouse blood and ongoing bacteremia to permit Ehrlichia acquisition by ticks. This study provides new insights into the importance of bacterial factors in regulating bacteremia, which may facilitate tick acquisition of pathogens.

Anaplasma phagocytophilum infection associated with strong inflammatory response in 3 cats.

Anaplasmosis is a vector-borne disease caused by Anaplasma (A.) spp. which currently is still rarely diagnosed in cats. This article describes 3 independent cases of anaplasmosis in cats from different regions of Germany presented to veterinarians in 2021. All cats showed unspecific clinical signs, such as fever, reduced general condition, and decreased appetite. One cat additionally had generalized limb pain, another showed reluctance to move as well as vomiting. On complete blood cell count, only 1 of 3 cats showed mild thrombocytopenia. A. phagocytophilum was detected in blood samples of all 3 cats by polymerase chain reaction. Additionally, in 2 cats (in which blood smears were evaluated) morulae could be detected within neutrophilic granulocytes. Initially, all 3 cats had highly elevated serum amyloid A (SAA) concentrations. Treatment with doxycycline caused a rapid improvement of clinical signs, followed by a decrease of SAA concentrations to normal levels as well as negative PCR results after a treatment duration of at least 28 days. In cats with fever, otherwise unspecific clinical signs with only mild or no hematological changes, elevated SAA concentrations, and previous exposure to ticks, attending veterinarians should consider anaplasmosis as differential diagnosis.

A canine case of Ehrlichia canis infection without a history of being in an endemic area in Japan.

A mixed-breed, 8-year-old male dog developed neutropenia, thrombocytopenia, and hyperglobulinemia. Bone marrow hyperplasia and splenic plasmacytosis were cytologically observed. The dog had never been outside of Tokyo or Shizuoka Prefecture. Splenectomy was performed to confirm and remove the cause of splenic plasmacytosis. A histopathological diagnosis of splenic plasmacytoma was made; however, serum protein electrophoresis showed polyclonal gammopathy. Further screening was performed, and Ehrlichia canis infection was confirmed. The dog was treated with doxycycline for 5 weeks. After the antibiotic therapy, no relapse of neutropenia, thrombocytopenia, hyperglobulinemia, or positive polymerase chain reaction result of E. canis infection was observed for 3 years. Careful attention should be given to ehrlichiosis when exploring the cause of pancytopenia or hyperglobulinemia, regardless of the travel history.

Five human pathogens detected by tick surveillance in New York City parks, 2014-2015.

A total of 2,504 ticks of 5 species (Ixodes scapularis, Dermacentor variabilis, Amblyomma americanum, Haemaphysalis leporispalustris, and H. longicornis) were collected over 2 yr (2014-2015) in New York City parks. Specimens were collected via tick-dragging, identified to species, and tested for pathogens of human diseases. The causative agents of 5 human diseases (Lyme borreliosis, ehrlichiosis, babesiosis, anaplasmosis, and Rocky Mountain spotted fever) were detected in a subset of samples. Results of this surveillance effort further illustrate that risk of tick-borne disease is considerable even in parks located adjacent to densely populated areas.

Prevalence of subclinical infectious agents in a blood donor population tested on every donation.

OBJECTIVES: This study aimed to assess the prevalence of blood-borne infectious agents in healthy, client-owned dogs from a blood donor population in Portugal and Spain, and to address the importance of a screening protocol on every donation. MATERIALS AND METHODS: Client-owned healthy dogs were tested before each donation on a veterinary blood bank. Blood samples from new potential donors, and from regular donors, were tested by real-time polymerase chain reaction for Leishmania species, Ehrlichia species, Brucella species, Babesia species and Anaplasma species Serological tests were also performed for Leishmania species, Ehrlichia species and Dirofilaria immitis. All donors were tested for every infectious agent in each donation. RESULTS: The study found that out of a total of 8036 donors and 35,120 samples tested, 3.9% of blood donors tested positive for at least one of the agents, with the most prevalent being Anaplasma species (2.1%). Serological tests also revealed positive results in 14.0% of donors, with the highest percentage for Leishmania species (7.7%). Moreover, the study found that 28.2% of positive results were from dogs with negative results in donations performed 3 to 12 months before, and 18.0% of positive results were recent infections. CLINICAL SIGNIFICANCE: These findings indicate a high prevalence of infectious agents in seemingly healthy, selected dogs eligible to become blood donors in the Iberian Peninsula, highlighting the importance of regular testing on every donation. This study emphasises the importance of a regular screening protocol for every donation instead of annual testing, as is commonly performed in veterinary medicine.

High prevalence of asymptomatic Anaplasma spp. infection in school-aged children in southeastern Gabon.

OBJECTIVES: The objective of this study was to evaluate the detection rates of asymptomatic Anaplasma spp. and Ehrlichia spp. infections in children in southeastern Gabon. METHODS: We conducted a cross-sectional study among school-aged children in southeastern Gabon between May and June 2021. Blood samples were collected. Anaplasmataceae, Anaplasma spp., and Ehrlichia spp. were detected by microscopy and polymerase chain reaction. RESULTS: Of the 452 blood samples collected, 57.5% (n/N=260/452) of the samples were positive for Anaplasma spp. and/or Ehrlichia spp. by microscopy, 86.9% (n/N=393/452) of the samples were positive for both Anaplasmataceae and Anaplasma spp., and none of the samples were found positive for Ehrlichia spp. PCR was more sensitive and specific than microscopy for detection of Anaplasma spp.. CONCLUSIONS: In our study, a significant number of positive blood samples for Anaplasma spp. were found in school-aged children in southeastern Gabon. Further studies are needed to determine the prevalence of different species of Anaplasma, their pathogenicity, and their transmission patterns.

Molecular Evidence of Ehrlichia canis (Rickettsiales: Anaplasmataceae) in Ticks (Ixodida: Ixodidae) Associated with Dogs (Carnivora: Canidae) from Nuevo Leon, Mexico.

Background: Ehrlichia canis is transmitted by ticks causing Canine monocytic ehrlichiosis, which is considered one of the most critical tickborne pathogens. Materials and Methods: This study aimed to identify by PCR technique E. canis in ticks associated with dogs from urban and rural homes in Nuevo Leon, Mexico. The study was conducted at 13 localities in eight municipalities from 2012 to 2021. Results: A total of 1873 ticks of three species were captured: Amblyomma tenellum, Dermacentor variabilis, and Rhipicephalus sanguineus s.l. The overall infection rate of E. canis in ticks was 59.12% (149/252). Of the 15 sequences, three haplotypes were identified. Conclusion: The urban transmission cycle of canine ehrlichiosis is demonstrated, where the potential vector is the tick R. sanguineus s.l.

Common and atypical presentations of Anaplasma phagocytophilum infection in equids with emphasis on neurologic and muscle disease.

BACKGROUND: Comprehensive descriptions of equids with granulocytic anaplasmosis (EGA) with neurologic or muscle disease and other atypical presentations are scarce in the literature. OBJECTIVE: Describe the clinical signs, laboratory findings, treatment, and outcome of equids with EGA with emphasis on neurologic and muscle disease. ANIMALS: Thirty-eight horses, 1 donkey. METHODS: Retrospective study. Equids with EGA were included. The electronic data base was searched from January 2000 to December 2022 using the words anaplasmosis, ehrlichiosis, granulocytic, and rickettsia. Signalment and clinical data were reviewed. Data were evaluated for normality using Shapiro-Wilk test. Parametric and nonparametric statistics were used for normally and non-normally distributed data. RESULTS: Common (41%) and other (59%) presentations were seen in horses ≥ 4 years of age (median, 14 years) with an overrepresentation of males (77%). Neurologic disease was common (41%), mainly presenting as diffuse symmetrical proprioceptive ataxia. Brain disease was less common manifesting as obtundation and cranial nerve deficits. Muscle disease was less common, with QH breeds with the variant causing myosin heavy chain myopathy (MYHM) having severe disease. Cavitary effusion, cardiomyopathy and disseminated intravascular coagulation (DIC) were uncommon. Clinical laboratory results varied depending on disease stage. Muscle enzyme activities were significantly higher in horses with muscle disease. Outcome was favorable with prompt tetracycline treatment. Death and long-term sequelae were not reported. CONCLUSIONS AND CLINICAL IMPORTANCE: Common and atypical presentations of EGA have a favorable outcome with prompt tetracycline treatment. Quarter horse breeds with muscle disease should be genotyped for MYHM.

Ehrlichia chaffeensis Co-Opts Phagocytic Hemocytes for Systemic Dissemination in the Lone Star Tick, Amblyomma americanum.

INTRODUCTION: Hematophagous arthropods can acquire and transmit several pathogens of medical importance. In ticks, the innate immune system is crucial in the outcome between vector-pathogen interaction and overall vector competence. However, the specific immune response(s) elicited by the immune cells known as hemocytes remains largely undefined in Ehrlichia chaffeensis and its competent tick vector, Amblyomma americanum. METHODS: We utilized injection of clodronate liposome to deplete tick granulocytes combined with infection with E. chaffeensis to demonstrate their essential role in microbial infection. RESULTS: Here, we show that granulocytes, professional phagocytic cells, are integral in eliciting immune responses against commensal and pathogen infection. The chemical depletion of granulocytes led to decreased phagocytic efficiency of tissue-associated hemocytes. We demonstrate that E. chaffeensis can infect circulating hemocytes, and both cell-free plasma and hemocytes from E. chaffeensis-infected ticks can establish Ehrlichia infection in recipient ticks. Lastly, we provide evidence to show that granulocytes play a dual role in E. chaffeensis infection. Depleting granulocytic hemocytes increased Ehrlichia load in the salivary gland and midgut tissues. In contrast, granulocyte depletion led to a reduced systemic load of Ehrlichia. CONCLUSION: This study has identified multiple roles for granulocytic hemocytes in the control and systemic dissemination of E. chaffeensis infection.

Novel renal injury markers in dogs with ehrlichiosis.

Canine monocytic ehrlichiosis (CME) has been observed to impact renal function. Currently, the recognition of acute kidney injury is through the nonspecific biomarker serum creatinine (sCr). Novel markers of renal injury such as urinary clusterin (uClust) and urinary cystatin B (uCysB) may increase our understanding of the relationship between ehrlichiosis and renal cellular injury. The aim of this study was to evaluate novel renal injury biomarkers in dogs with acute CME. Twenty healthy dogs were enrolled in the control group (CG), and 16 dogs naturally infected with Ehrlichia canis were included in the Ehrlichia Group (EG). All dogs were followed for 45 days. EG dogs were treated with doxycycline twice daily for the first 30 days. Urine and serum were collected at: 0, 0.5, 1, 15, 30, and 45 days after start of treatment. Urine concentrations of uClust and uCysB were determined using a research ELISA immunoassay. A linear mixed model was used to estimate population mean of renal injury markers with patient as the random effect, and day and treatment as fixed effects. EG was observed to have higher uClust values compared to CG (estimated population mean EG: 213 ng/dL vs. CG: 84 ng/dL, P < 0.001). EG was observed to have higher uCysB values compared to CG (estimated population mean EG: 248 ng/dL vs. CG: 38 ng/dL, P < 0.001). Increases in uCysB and uClust suggest the presence of renal injury and a possible mechanism for the observed predisposition to chronic kidney disease in dogs with ehrlichiosis.

Mathematical model of Ehrlichia chaffeensis transmission dynamics in dogs.

Ehrlichia chaffeensis is a tick-borne disease transmitted by ticks to dogs. Few studies have mathematical modelled such tick-borne disease in dogs, and none have developed models that incorporate different ticks' developmental stages (discrete variable) as well as the duration of infection (continuous variable). In this study, we develop and analyze a model that considers these two structural variables using integrated semigroups theory. We address the well-posedness of the model and investigate the existence of steady states. The model exhibits a disease-free equilibrium and an endemic equilibrium. We calculate the reproduction number (T0). We establish a necessary and sufficient condition for the bifurcation of an endemic equilibrium. Specifically, we demonstrate that a bifurcation, either backward or forward, can occur at T0=1, leading to the existence, or not, of an endemic equilibrium even when T0<1. Finally, numerical simulations are employed to illustrate these theoretical findings.

Clinical and pathological factors associated with Ehrlichia canis in companion dogs.

INTRODUCTION: Canine monocytic ehrlichiosis (CME) is a disease caused by the Gram-negative bacteria Ehrlichia canis, a bacterium that affects domestic dogs but can also infect humans. The diagnosis implies a challenge due to its diversity in clinical manifestations. METHODOLOGY: The frequency of E. canis infection, risk factors, and clinical-pathological parameters associated with seropositivity were calculated with the PROC FREQ TABLES and PROC LOGISTIC procedures of the SAS statistical software. RESULTS: The study showed a seroprevalence of 26.62% (156/586). Association between seropositivity and risk factors was found. The age and the presence of ticks including clinical signs such as anorexia, seizures, cough, petechiae, epistaxis, and hematochezia, as well as multiple blood and biochemical alterations were analyzed. The logistic regression analysis showed a high predictive power (c = 0.98) for CME for thrombocytopenia, leukopenia, and anemia. CONCLUSIONS: The high prevalence of E. canis in endemic areas makes its diagnosis difficult. Thus, clinical signs must be considered, along with blood and biochemical alterations, as a possible predictor of the disease.

Hepatocyte-specific regulation of autophagy and inflammasome activation via MyD88 during lethal Ehrlichia infection.

Hepatocytes play a crucial role in host response to infection. Ehrlichia is an obligate intracellular bacterium that causes potentially life-threatening human monocytic ehrlichiosis (HME) characterized by an initial liver injury followed by sepsis and multi-organ failure. We previously showed that infection with highly virulent Ehrlichia japonica (E. japonica) induces liver damage and fatal ehrlichiosis in mice via deleterious MyD88-dependent activation of CASP11 and inhibition of autophagy in macrophage. While macrophages are major target cells for Ehrlichia, the role of hepatocytes (HCs) in ehrlichiosis remains unclear. We investigated here the role of MyD88 signaling in HCs during infection with E. japonica using primary cells from wild-type (WT) and MyD88-/- mice, along with pharmacologic inhibitors of MyD88 in a murine HC cell line. Similar to macrophages, MyD88 signaling in infected HCs led to deleterious CASP11 activation, cleavage of Gasdermin D, secretion of high mobility group box 1, IL-6 production, and inflammatory cell death, while controlling bacterial replication. Unlike macrophages, MyD88 signaling in Ehrlichia-infected HCs attenuated CASP1 activation but activated CASP3. Mechanistically, active CASP1/canonical inflammasome pathway negatively regulated the activation of CASP3 in infected MyD88-/- HCs. Further, MyD88 promoted autophagy induction in HCs, which was surprisingly associated with the activation of the mammalian target of rapamycin complex 1 (mTORC1), a known negative regulator of autophagy. Pharmacologic blocking mTORC1 activation in E. japonica-infected WT, but not infected MyD88-/- HCs, resulted in significant induction of autophagy, suggesting that MyD88 promotes autophagy during Ehrlichia infection not only in an mTORC1-indpenedent manner, but also abrogates mTORC1-mediated inhibition of autophagy in HCs. In conclusion, this study demonstrates that hepatocyte-specific regulation of autophagy and inflammasome pathway via MyD88 is distinct than MyD88 signaling in macrophages during fatal ehrlichiosis. Understanding hepatocyte-specific signaling is critical for the development of new therapeutics against liver-targeting pathogens such as Ehrlichia.