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Cellular Microbiology Sep 2021Toll-like receptors (TLRs) are a class of membrane-spanning proteins of host cells. TLR2 and TLR4 are displayed on the surface of macrophages, neutrophils and dendritic...
Toll-like receptors (TLRs) are a class of membrane-spanning proteins of host cells. TLR2 and TLR4 are displayed on the surface of macrophages, neutrophils and dendritic cells and recognise structurally conserved microbial signatures defined as Pathogen associated molecular patterns (PAMPs). C3H mice are susceptible to tick-borne pathogens; Lyme disease causing Borrelia burgdorferi that manifests arthritis and carditis and Apicomplexan protozoan, Babesia microti (Bm) that causes significant parasitemia associated with erythrocytopenia and haemoglobinuria. B. burgdorferi lacks typical TLR4 ligand lipopolysaccharides (LPS) and Bm TLR ligand(s) remain unknown. Only Borrelia lipoproteins that signal through TLR2 are established as PAMPs of these pathogens for TLR2/TLR4. Infection of C3H mice with each pathogen individually resulted in increase in the percentage of splenic B, T and FcR+ cells while their co-infection significantly diminished levels of these cells and caused increased B. burgdorferi burden in the specific organs. The most pronounced inflammatory arthritis was observed in co-infected C3H/HeJ mice. Parasitemia levels and kinetics of resolution of Bm in both mice strains were not significantly different. Transfected HEK293 cells showed pronounced signalling by B. burgdorferi through TLR2 and to some extent by TLR4 while Bm and infected erythrocytes did not show any response confirming our results in mice.
Topics: Animals; Babesia microti; Babesiosis; Borrelia burgdorferi; HEK293 Cells; Humans; Lyme Disease; Mice; Mice, Inbred C3H; Toll-Like Receptor 4
PubMed: 33938125
DOI: 10.1111/cmi.13350 -
Parasites & Vectors Jun 2023Babesia spp. are intraerythrocytic apicomplexans that digest and utilize red blood cells in a similar way to intraerythrocytic Plasmodium spp., but unlike the latter,...
Babesia spp. are intraerythrocytic apicomplexans that digest and utilize red blood cells in a similar way to intraerythrocytic Plasmodium spp., but unlike the latter, are not sensitive to artemisinin. A comparison of Babesia and Plasmodium genomes revealed that Babesia genomes, which are smaller than those of Plasmodium, lack numerous genes, and especially haem synthesis-related genes, that are found in the latter. Single-cell sequencing analysis showed that the different treatment groups of Babesia microti with expressed pentose phosphate pathway-related, DNA replication-related, antioxidation-related, glycolysis-related, and glutathione-related genes were not as sensitive to artemether as Plasmodium yoelii 17XNL. In particular, pentose phosphate pathway-related, DNA replication-related, and glutathione-related genes, which were actively expressed in P. yoelii 17XNL, were not actively expressed in B. microti. Supplying iron in vivo can promote the reproduction of B. microti. These results suggest that Babesia spp. lack a similar mechanism to that of malaria parasites through which the haem or iron in hemoglobin is utilized, and that this likely leads to their insensitivity to artemisinin.
Topics: Humans; Babesia; Artemisinins; Plasmodium yoelii; Iron; Heme; Babesiosis
PubMed: 37291657
DOI: 10.1186/s13071-023-05783-4 -
Frontiers in Cellular and Infection... 2022Babesiosis causes high morbidity and mortality in immunocompromised individuals. An earlier study suggested that lethal infection in murine can be evaded by primary...
Babesiosis causes high morbidity and mortality in immunocompromised individuals. An earlier study suggested that lethal infection in murine can be evaded by primary infection activated macrophage-based immune response during the chronic stage of infection. However, whether the same immune dynamics occur during acute co-infection is not known. Hence, we used the mouse model to investigate the host immunity during simultaneous acute disease caused by two species of different pathogenicity. Results showed that primary infection attenuated parasitemia and conferred immunity in challenge-infected mice as early as day 4 post-primary infection. Likewise, acute co-infection undermined the splenic immune response, characterized by the significant decrease in splenic B and T cells leading to the reduction in antibody levels and decline in humoral immunity. Interestingly, increased macrophage and natural killer splenic cell populations were observed, depicting their subtle role in the protection. Pro-inflammatory cytokines (i.e. IFN-γ, TNF-α) were downregulated, while the anti-inflammatory cytokine IL-10 was upregulated in mouse sera during the acute phase of co-infection. Herein, the major cytokines implicated in the lethality caused by infection were IFN- γ and IL-10. Surprisingly, significant differences in the levels of serum IFN- γ and IL-10 between co-infected survival groups (day 4 and 6 challenge) indicated that even a two-day delay in challenge infection was crucial for the resulting pathology. Additionally, oxidative stress in the form of reactive oxygen species contributed to the severity of pathology during acute babesiosis. Histopathological examination of the spleen showed that the erosion of the marginal zone was more pronounced during infection, while the loss of cellularity of the marginal zone was less evident during co-infection. Future research warrants investigation of the roles of various immune cell subtypes in the mechanism involved in the protection of co-infected hosts.
Topics: Animals; Babesia; Babesiosis; Coinfection; Cytokines; Infections; Interferon-gamma; Interleukin-10; Mice; Mice, Inbred BALB C
PubMed: 35719355
DOI: 10.3389/fcimb.2022.885985 -
Frontiers in Microbiology 2022is the dominant species responsible for human babesiosis, which is associated with severe hemolytic anemia and splenomegaly because it infects mammalian erythrocytes....
INTRODUCTION
is the dominant species responsible for human babesiosis, which is associated with severe hemolytic anemia and splenomegaly because it infects mammalian erythrocytes. The actual prevalence of is thought to have been substantially underestimated.
METHODS
In this study, Bagg's albino/c (BALB/c) mice were intraperitoneally injected with -infected erythrocytes, and parasitemia was subsequently measured by calculating the proportion of infected erythrocytes. The ultrastructure of infected erythrocytes was observed using scanning and transmission electron microscopes. Quantifying phosphatidylserine (PS) exposure, oxidative stress, intracellular Ca, and erythropoiesis of erythrocytes were done using flow cytometry. The physiological indicators were analyzed using a Mindray BC-5000 Vet automatic hematology analyzer.
RESULTS
Of note, 40.7 ± 5.9% of erythrocytes changed their structure and shrunk in the -infected group. The percentage of annexin V-positive erythrocytes and the levels of reactive oxygen species (ROS) in the erythrocytes were higher in the -infected group than in the control group at 10 dpi. Significant splenomegaly and severe anemia were also observed following infection. The parasitemia level in the -infected splenectomized group was higher than that of the -infected sham group. The population of early erythroblasts increased, and the late erythroblasts decreased in both the bone marrow and spleen tissues of the -infected group at 10 dpi.
DISCUSSION
PS exposure and elevated ROS activities were hallmarks of eryptosis in the -infected group. This study revealed for the first time that could also induce eryptosis. At the higher parasitemia phase, the occurrence of severe anemia and significant changes in the abundance of erythroblasts in -infected mice group were established. The spleen plays a critical protective role in controlling infection and preventing anemia. infection could cause a massive loss of late erythroblasts and induce erythropoiesis.
PubMed: 36687590
DOI: 10.3389/fmicb.2023.1083467 -
Frontiers in Cellular and Infection... 2022Babesiosis is a zoonosis and an important blood-borne human parasitic infection that has gained attention because of its growing infection rate in humans by transfer...
Babesiosis is a zoonosis and an important blood-borne human parasitic infection that has gained attention because of its growing infection rate in humans by transfer from animal reservoirs. represents a potential threat to the blood supply because asymptomatic infections in man are common, and blood from such donors can cause severe disease in certain recipients. Extracellular vesicles (EVs) are vesicles released by cells that contain a complex mixture of proteins, lipids, glycans, and genetic information that have been shown to play important roles in disease pathogenesis and susceptibility, as well as cell-cell communication and immune responses. In this article, we report on the identification and characterization of EVs released from red blood cells (RBCs) infected by two major human species- from culture and those from an mouse infection. Using nanoparticle tracking analysis, we show that there is a range of vesicle sizes from 30 to 1,000 nm, emanating from the -infected RBC. The study of these EVs in the context of hemoparasite infection is complicated by the fact that both the parasite and the host RBC make and release vesicles into the extracellular environment. However, the EV frequency is 2- to 10-fold higher in -infected RBCs than uninfected RBCs, depending on levels of parasitemia. Using parasite-specific markers, we were able to show that ~50%-60% of all EVs contained parasite-specific markers on their surface and thus may represent the specific proportion of EVs released by infected RBCs within the EV population. Western blot analysis on purified EVs from both and infections revealed several parasite proteins that were targets of the host immune response. In addition, microRNA analysis showed that infected RBC EVs have different microRNA signature from uninfected RBC EVs, indicating a potential role as disease biomarkers. Finally, EVs were internalized by other RBCs in culture, implicating a potential role for these vesicles in cellular communication. Overall, our study points to the multiple functional implications of EVs in -host interactions and support the potential that EVs have as agents in disease pathogenesis.
Topics: Humans; Mice; Animals; Babesia microti; Babesia; Erythrocytes; Extracellular Vesicles; MicroRNAs; Complex Mixtures; Lipids
PubMed: 36275032
DOI: 10.3389/fcimb.2022.962944 -
Annals of Clinical Microbiology and... Feb 2017Babesiosis, a zoonotic parasitic infection transmitted by the Ixodes tick, has become an emerging health problem in humans that is attracting attention worldwide. Most... (Review)
Review
BACKGROUND
Babesiosis, a zoonotic parasitic infection transmitted by the Ixodes tick, has become an emerging health problem in humans that is attracting attention worldwide. Most cases of human babesiosis are reported in the United States and Europe. The disease is caused by the protozoa of the genus Babesia, which invade human erythrocytes and lyse them causing a febrile hemolytic anemia. The infection is usually asymptomatic or self-limited in the immunocompetent host, or follows a persistent, relapsing, and/or life threatening course with multi-organ failure, mainly in the splenectomized or immunosuppressed patients. Hematologic manifestations of the disease are common. They can range from mild anemia, to severe pancytopenia, splenic rupture, disseminated intravascular coagulopathy (DIC), or even hemophagocytic lymphohistiocytosis (HLH).
CASE PRESENTATION
A 70 year old immunocompetent female patient living in New York City presented with a persistent fever, night sweats, and fatigue of 5 days duration. Full evaluation showed a febrile hemolytic anemia along with neutropenia and thrombocytopenia. Blood smear revealed intraerythrocytic Babesia, which was confirmed by PCR. Bone marrow biopsy was remarkable for dyserythropoiesis, suggesting possible HLH, supported by other blood workup meeting HLH-2004 trial criteria.
CONCLUSION
Human babesiosis is an increasing healthcare problem in the United States that is being diagnosed more often nowadays. We presented a case of HLH triggered by Babesia microti that was treated successfully. Also, we presented the hematologic manifestations of this disease along with their pathophysiologies.
Topics: Aged; Anemia, Hemolytic; Babesia; Babesiosis; Bone Marrow; Erythrocytes; Female; Fever; Humans; Immunocompetence; Neutropenia; New York City; Thrombocytopenia
PubMed: 28202022
DOI: 10.1186/s12941-017-0179-z -
Journal of Parasitology Research 2015Borrelia burgdorferi, the causative agent of Lyme disease, and Babesia microti, a causative agent of babesiosis, are increasingly implicated in the growing tick-borne... (Review)
Review
Borrelia burgdorferi, the causative agent of Lyme disease, and Babesia microti, a causative agent of babesiosis, are increasingly implicated in the growing tick-borne disease burden in the northeastern United States. These pathogens are transmitted via the bite of an infected tick vector, Ixodes scapularis, which is capable of harboring and inoculating a host with multiple pathogens simultaneously. Clinical presentation of the diseases is heterogeneous and ranges from mild flu-like symptoms to near-fatal cardiac arrhythmias. While the reason for the variability is not known, the possibility exists that concomitant infection with both B. burgdorferi and B. microti may synergistically increase disease severity. In an effort to clarify the current state of understanding regarding coinfection with B. burgdorferi and B. microti, in this review, we discuss the geographical distribution and pathogenesis of Lyme disease and babesiosis in the United States, the immunological response of humans to B. burgdorferi or B. microti infection, the existing knowledge regarding coinfection disease pathology, and critical factors that have led to ambiguity in the literature regarding coinfection, in order to eliminate confusion in future experimental design and investigation.
PubMed: 26697208
DOI: 10.1155/2015/587131 -
Parasites & Vectors Mar 2021Protozoa in the genus Babesia are transmitted to humans through tick bites and cause babesiosis, a malaria-like illness. Vertical transmission of Babesia spp. has been...
BACKGROUND
Protozoa in the genus Babesia are transmitted to humans through tick bites and cause babesiosis, a malaria-like illness. Vertical transmission of Babesia spp. has been reported in mammals; however, the exact timing and mechanisms involved are not currently known. The aims of this study were to evaluate the success of vertical transmission of B. microti in female mice infected before pregnancy (mated during the acute or chronic phases of Babesia infection) and that of pregnant mice infected during early and advanced pregnancy; to evaluate the possible influence of pregnancy on the course of parasite infections (parasitaemia); and to assess pathological changes induced by parasitic infection.
METHODS
The first set of experiments involved two groups of female mice infected with B. microti before mating, and inseminated on the 7th day and after the 40th day post infection. A second set of experiments involved female mice infected with B. microti during pregnancy, on the 4th and 12th days of pregnancy. Blood smears and PCR targeting the 559 bp 18S rRNA gene fragment were used for the detection of B. microti. Pathology was assessed histologically.
RESULTS
Successful development of pregnancy was recorded only in females mated during the chronic phase of infection. The success of vertical transmission of B. microti in this group was 63%. No evidence of pregnancy was found in females mated during the acute phase of infection or on the 4th day of pregnancy. In the group infected on the 12th day of pregnancy, numerous complications including loss of pregnancy and stillbirths were recorded. During the acute phase of infection, parasitaemia was lower in pregnant females in comparison to infected, non-pregnant control females.
CONCLUSIONS
Acute B. microti infection prevents the initiation of pregnancy and embryonic development if it occurs during the first trimester, and causes severe complications in foetal BALB/c mice in the second and third trimesters of pregnancy. Chronic B. microti infection has no detrimental impact on the initiation and development of pregnancy, but results in congenital infection of the offspring. Further study is required to determine the extent to which maternal anti-babesial immune responses contribute to compromise pregnancy in the murine model of congenital Babesia infection.
Topics: Animals; Babesia microti; Babesiosis; Disease Models, Animal; Embryonic Development; Female; Infectious Disease Transmission, Vertical; Male; Mice; Mice, Inbred BALB C; Parasitemia; Pregnancy; RNA, Ribosomal, 18S
PubMed: 33653384
DOI: 10.1186/s13071-021-04638-0 -
Parasites & Vectors Nov 2022Babesia is an intraerythrocytic parasite often misdiagnosed as a malaria parasite, leading to inappropriate treatment of the disease especially in co-endemic areas. In...
BACKGROUND
Babesia is an intraerythrocytic parasite often misdiagnosed as a malaria parasite, leading to inappropriate treatment of the disease especially in co-endemic areas. In recent years, optical diffraction tomography (ODT) has shown great potential in the field of pathogen detection by quantification of three-dimensional (3D) imaging tomograms. The 3D imaging of biological cells is crucial to investigate and provide valuable information about the mechanisms behind the pathophysiology of cells and tissues.
METHODS
The early ring stage of P. falciparum were obtained from stored stock of infected RBCs and of B. microti were obtained from infected patients during diagnosis. The ODT technique was applied to analyze and characterize detailed differences between P. falciparum and B. microti ring stage at the single cell level. Based on 3D quantitative information, accurate measurement was performed of morphological, biochemical, and biophysical parameters.
RESULTS
Accurate measurements of morphological parameters indicated that the host cell surface area at the ring stage in B. microti was significantly smaller (140.2 ± 17.1 µm) than that in P. falciparum (159.0 ± 15.2 µm), and sphericities showed higher levels in B. microti-parasitized cells (0.66 ± 0.05) than in P. falciparum (0.60 ± 0.04). Based on biochemical parameters, host cell hemoglobin level was significantly higher and membrane fluctuations were respectively more active in P. falciparum-infected cells (30.25 ± 2.96 pg; 141.3 ± 24.68 nm) than in B. microti (27.28 ± 3.52 pg; 110.1 ± 38.83 nm). The result indicates that P. falciparum more actively altered host RBCs than B. microti.
CONCLUSION
Although P. falciparum and B. microti often show confusable characteristics under the microscope, and the actual three-dimensional properties are different. These differences could be used in differential clinical diagnosis of erythrocytes infected with B. microti and P. falciparum.
Topics: Humans; Plasmodium falciparum; Babesia microti; Malaria, Falciparum; Erythrocytes; Babesia
PubMed: 36397133
DOI: 10.1186/s13071-022-05569-0 -
Longhua Chinese Medicine Jun 2021L.is a well-established medicinal herb used for millennia to treat parasites and fever-related ailments caused by various microbes. Although effective against many...
BACKGROUND
L.is a well-established medicinal herb used for millennia to treat parasites and fever-related ailments caused by various microbes. Although effective against many infectious agents, the plant is not a miracle cure and there are infections where it has proved ineffective or limited. It is important to report those failures.
METHODS
Here artemisinin, artesunate and dried leaf slurries of were used daily for 6 days against in mice 2 days post infection at 100 µg artemisinin/kg body weight. Parasitemia was measure before and 15 days days post treatment. Artemisinin and extracts of also were tested against six sp. at artemisinin concentrations up to 180 µM and growth measured after cultures were fed drugs once at different stages of growth and also after repeated dosing.
RESULTS
, artesunate, and artemisinin were ineffective in reducing or eliminating parasitemia in -infected mice treated at 100 µg artemisinin/kg body weight. Although the growth of exponential cultures of many of the tested sp. was inhibited, the response was not sustained and both artemisinin and were essentially ineffective at concentrations of artemisinin at up to 180 µM of artemisinin.
CONCLUSIONS
Together these results show that artemisinin, its derivatives, and are ineffective against and at least six species of .
PubMed: 34316676
DOI: 10.21037/lcm-21-2