Effects of radiation on the fitness, sterility and arbovirus susceptibility of a Wolbachia-free Aedes albopictus strain for use in the sterile insect technique.

BACKGROUND: The sterile insect technique (SIT) is a green and species-specific insect pest control technique that suppresses target populations by releasing factory-reared, radiosterilized males into the wild. Once released, it is important to be able to distinguish the released males from the wild males for monitoring purposes. Several methods to mark the sterile males exist. However, most have limitations due to monetary, process efficiency, or insect quality. Aedes albopictus is naturally infected with Wolbachia at a high prevalence, therefore the elimination of Wolbachia can serve as a biomarker to distinguish factory-reared male mosquitoes from wild conspecifics. RESULTS: In this study, a Wolbachia-free Ae. albopictus GT strain was developed and its fitness evaluated, which was found to be comparable to the wild GUA strain. In addition, GT male mosquitoes were irradiated at the adult stage and a dose of 20 Gy or more induced over 99% sterility. Moreover, a dose of 30 Gy (almost completely sterilizing male and female mosquitoes) had limited effects on the mating competitiveness of GT males and the vector competence of GT females, respectively. However, radiation reduced mosquito longevity, regardless of sex. CONCLUSION: Our results indicate that the Ae. albopictus GT strain can be distinguished from wild mosquitoes based on Wolbachia status and shows similar fitness, radio-sensitivity and arbovirus susceptibility to the GUA strain, indicating that it is feasible to use the GT strain to suppress Ae. albopictus populations for SIT programmes. © 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

MicroRNAs: protective regulators for neuron growth and development.

MicroRNAs (miRNAs) play an important regulatory role in neuronal growth and development. Different miRNAs target different genes to protect neurons in different ways, such as by avoiding apoptosis, preventing degeneration mediated by conditional mediators, preventing neuronal loss, weakening certain neurotoxic mechanisms, avoiding damage to neurons, and reducing inflammatory damage to them. The high expression of miRNAs in the brain has significantly facilitated their development as protective targets for therapy, including neuroprotection and neuronal recovery. miRNA is indispensable to the growth and development of neurons, and in turn, is beneficial for the development of the brain and checking the progression of various diseases of the nervous system. It can thus be used as an important therapeutic target for models of various diseases. This review provides an introduction to the protective effects of miRNA on neurons in case of different diseases or damage models, and then provides reference values and reflections on the relevant treatments for the benefit of future research in the area.

iNOS is essential to maintain a protective Th1/Th2 response and the production of cytokines/chemokines against Schistosoma japonicum infection in rats.

Humans and a wide range of mammals are generally susceptible to Schistosoma infection, while some rodents such as Rattus rats and Microtus spp are not. We previously demonstrated that inherent high expression levels of nitric oxide (NO), produced by inducible nitric oxide synthase (iNOS), plays an important role in blocking the growth and development of Schistosoma japonicum in wild-type rats. However, the potential regulatory effects of NO on the immune system and immune response to S. japonicum infection in rats are still unknown. In this study, we used iNOS-knockout (KO) rats to determine the role of iNOS-derived NO in the immune system and immunopathological responses to S. japonicum infection in rats. Our data showed that iNOS deficiency led to weakened immune activity against S. japonicum infection. This was characterized by the impaired T cell responses and a significant decrease in S. japonicum-elicited Th2/Th1 responses and cytokine and chemokine-producing capability in the infected iNOS-KO rats. Unlike iNOS-KO mice, Th1-associated cytokines were also decreased in the absence of iNOS in rats. In addition, a profile of pro-inflammatory and pro-fibrogenic cytokines was detected in serum associated with iNOS deficiency. The alterations in immune responses and cytokine patterns were correlated with a slower clearance of parasites, exacerbated granuloma formation, and fibrosis following S. japonicum infection in iNOS-KO rats. Furthermore, we have provided direct evidence that high levels of NO in rats can promote the development of pulmonary fibrosis induced by egg antigens of S. japonicum, but not inflammation, which was negatively correlated with the expression of TGF-ß3. These studies are the first description of the immunological and pathological profiles in iNOS-KO rats infected with S. japonicum and demonstrate key differences between the responses found in mice. Our results significantly enhance our understanding of the immunoregulatory effects of NO on defensive and immunopathological responses in rats and the broader nature of resistance to pathogens such as S. japonicum.

A restored humoral environment ameliorates acute brain injury after Angiostrongylus cantonensis infection.

Circulating factors in the circulatory system support important functions of living tissues and the body. Parabiosis is a condition in which two living animals are connected using surgical methods and share a single circulatory system. Angiostrongylus cantonensis is the major cause of infectious eosinophilic meningitis, which causes severe damage to the central nervous system (CNS) and immune system. However, the mechanism of immunopathology remains largely unknown. We hypothesize that a restored humoral environment can help relieve damage to the CNS and immune system. In the present study, we found that administration of normal serum significantly reduced mortality, alleviated thymic atrophy and reduced inflammation in the brains of mice infected with A. cantonensis. We further generated parabiotic pairs between two healthy mice, one of which was then orally infected with A. cantonensis. The results showed that compared with singleton mice, mice connected with a healthy parabiotic partner were protected against CNS and immune system damage, as revealed by significantly reduced inflammation in the brain, alleviated thymic atrophy, and decreased expression of proinflammatory cytokines. These findings revealed that a healthy systemic environment can relieve damage to the CNS and immune system in infected mice, suggesting novel therapeutic approaches for diseases involving severe brain and immune system damage.

Interleukin 17A Derived from γδ T Cell Induces Demyelination of the Brain in Angiostrongylus cantonensis Infection.

Angiostrongylus cantonensis infection is a typical cause of eosinophilic encephalitis (EM), which has been reported to induce serious damage in the central nervous system. Both parasite and host factors contribute to the onset of EM, but the related immune-inflammation pathogenesis remains poorly characterised. An A. cantonensis infection model was generated through the infection of mice by gavage. Transmission electron microscopy and immunohistochemistry were used to assess the pathologic changes in the brain. The mRNA expression of inflammatory factors was tested using qRT-PCR. A combination of flow cytometry and western blotting was used to evaluate the alteration of leukocytes and related cytokines. A critical role of IL-17 was found by injecting IL-17A monoclonal antibody into naïve and A. cantonensis-infected mice. A. cantonensis larvae altered the immune homeostasis in the brain, leading to the destruction of myelin sheaths and activation of microglia and macrophage. During this process, IL-17A accumulation was observed, and IL-17RA was expressed in oligodendrocytes and microglia during the infection. Notably, γδ T cell was the major origin of IL-17A production induced by the parasite. After an IL-17A-neutralising antibody was applied, alterations in myelination and the state of the microglia/macrophage were discovered; the neurobehavioural scores of the mice also improved. Our study reveals one unrecognised impact of the γδ T cells in parasitic encephalopathy and emphasises that blocking IL-17A signalling can attenuate microglia and macrophage activation, thus reducing CNS demyelination and ameliorating the neurobehavioural deficit in A. cantonensis-infected mice.

Recombinant protein Schistosoma japonicum-derived molecule attenuates dextran sulfate sodium-induced colitis by inhibiting miRNA-217-5p to alleviate apoptosis.

BACKGROUND: Inflammatory bowel disease (IBD) affects millions of people worldwide and has emerged as a growing problem in industrialized nations. The lack of therapeutic targets has limited the treatment of IBD. Studies found that parasitic nematode infections can ameliorate clinical and experimental colitis. Our previous study found that rSj16, a 16-kDa secreted protein of Schistosoma japonicum produced by Escherichia coli, has protective effects on dextran sulfate sodium (DSS)-induced colitis in mice. Apoptosis is an important factor in the pathogenesis of colitis. However, it is not clear whether the effect of rSj16 on colitis is related to apoptosis. AIM: To investigate whether the protective effects of rSj16 on colitis is related to apoptosis and its mechanism. METHODS: In-vivo , colitis was induced by DSS. The severity of colitis was assessed. WB was used to detect the changes of apoptosis-related genes in colon tissues. Q-PCR was used to detect the changes of miRNA-217-5p and HNF1B. In-vitro , WB was used to detect the changes of apoptosis-related genes in intestinal epithelial cells. TUNNEL staining and flow cytometry were used to detect cell apoptosis. RESULTS: rSj16 attenuates clinical activity in DSS-induced colitis mice. TUNNEL staining and WB results showed that apoptosis was increased in colon tissue after treatment with DSS, and the apoptosis of colon tissue was significantly reduced after treatment with rSj16. Compared with normal mice, the expression of miR-217-5p was increased in colon tissue of DSS-induced colitis mice. In addition, the miR-217-5p target gene hnf1b was decreased after administration of DSS. After treatment with rSj16, the expression of miR-217-5p was decreased and the expression of HNF1B was increased compared with the DSS-treated group. When Etoposide was used in combination with miR-217-5p mimic on MODE-K cells, the expression of cleaved-Caspase-3 and Bax was increased, and Bcl-2 was decreased compared with only Etoposide treatment, the expression of HNF1B was significantly reduced, suggesting that miR-217-5p acts as a pro-apoptotic in colon epithelial cells and down-regulates the target gene hnf1b. After rSj16 administration in MODE-K cells, miR-217-5p expression was significantly decreased, HNF1B expression was increased, and apoptosis was reduced. CONCLUSION: The protective effects of rSj16 on colitis is related to apoptosis and miRNA-217-5p may be a further target for therapeutic intervention against IBD.

Diverse and abundant resistome in terrestrial and aquatic vertebrates revealed by transcriptional analysis.

Despite increasing evidence that antibiotic resistant pathogens are shared among humans and animals, the diversity, abundance and patterns of spread of antibiotic resistance genes (ARGs) in wildlife remains unclear. We identified 194 ARGs associated with phenotypic resistance to 13 types of antibiotic in meta-transcriptomic data generated from a broad range of lower vertebrates residing in both terrestrial and aquatic habitats. These ARGs, confirmed by PCR, included those that shared high sequence similarity to clinical isolates of public health concern. Notably, the lower vertebrate resistome varied by ecological niche of the host sampled. The resistomes in marine fish shared high similarity and were characterized by very high abundance, distinct from that observed in other habitats. An assessment of ARG mobility found that ARGs in marine fish were frequently co-localized with mobile elements, indicating that they were likely spread by horizontal gene transfer. Together, these data reveal the remarkable diversity and transcriptional levels of ARGs in lower vertebrates, and suggest that these wildlife species might play an important role in the global spread of ARGs.

Immunopathology in schistosomiasis is regulated by TLR2,4- and IFN-γ-activated MSC through modulating Th1/Th2 responses.

BACKGROUND AND AIMS: A marked egg-induced CD4+ T cell programmed inflammation and subsequent hepatic fibrosis characterize the pathogenesis of schistosomiasis. Mesenchymal stem cell (MSC) has been extensively studied for the treatment of schistosomiasis. However, the mechanism by which MSCs modulate the pathogenesis of schistosomiasis has not been clarified. Furthermore, the local inflammatory milieu may greatly influence the immunoregulatory properties of MSCs, and our early experiments demonstrated that Toll-like receptor (TLR)2/TLR4 agonist effected immune modulation of MSC. Here, we further investigated their modulation on the pathogenesis of schistosomiasis. METHODS: Adult BALB/c male mice were percutaneously infected with 16 ± 2 pairs S. japonicum cercariae and received intravenously pretreated MSC at 1 week and 3 weeks post-infection, respectively. At 8 weeks post-infection, effects of MSC on liver histology were shown by hematoxylin and eosin (H&E) staining and Masson staining and quantitatively compared by the hepatic hydroxyproline content; α-smooth muscle actin (α-SMA), collagen type I(Col-1), transforming growth factor ß (TGF-ß), and tumor necrosis factor-α (TNF-α) gene expression in the liver were assessed by semi-quantitative polymerase chain reaction (PCR); the Th1/Th2 dominance among different groups was compared by analyzing CD4+ interferon-γ (IFN-γ)+ and CD4+interleukin-4 (IL-4)+T cells in the liver by flow cytometry and serum level of IFN-γ and IL-5 using enzyme-linked immunosorbent assay (ELISA). Effects of different kinds of MSC were further evaluated in vitro by the coculture system. RESULTS: Results showed TLR4- and IFN-γ-activated MSC alleviated liver fibrosis in infected mice, without a significant increase of mortality, and unpretreated MSC showed no clear improvement; however, TLR2- and IFN-γ-activated MSC displayed aggravated immunopathology. In accord with the pathological results, TLR4- and IFN-γ-activated MSC groups showed moderate enhancement of Th1 response in vitro and clear Th1 dominance in vivo without leading to extreme inflammation, whereas TLR2- and IFN-γ-activated MSC not only induced Th1 response, but also triggered excessive inflammation as evidenced by atrophy of the thymus and higher TNF level in the coculture system. CONCLUSIONS: This study demonstrates that TLR4 combined with IFN-γ can activate the MSC group with positive effects on the pathology of schistosomiasis by modulating Th subsets at some degree. This result suggests that when MSC is being used to treat different immuno-disturbance complications, subtle pretreatment methods should be seriously considered.

Human African trypanosomiasis: the current situation in endemic regions and the risks for non-endemic regions from imported cases.

Human African trypanosomiasis (HAT) is caused by Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense and caused devastating epidemics during the 20th century. Due to effective control programs implemented in the last two decades, the number of reported cases has fallen to a historically low level. Although fewer than 977 cases were reported in 2018 in endemic countries, HAT is still a public health problem in endemic regions until it is completely eliminated. In addition, almost 150 confirmed HAT cases were reported in non-endemic countries in the last three decades. The majority of non-endemic HAT cases were reported in Europe, USA and South Africa, due to historical alliances, economic links or geographic proximity to disease-endemic countries. Furthermore, with the implementation of the 'Belt and Road' project, sporadic imported HAT cases have been reported in China as a warning sign of tropical diseases prevention. In this paper, we explore and interpret the data on HAT incidence and find no positive correlation between the number of HAT cases from endemic and non-endemic countries. This data will provide useful information for better understanding the imported cases of HAT globally in the post-elimination phase.

Fighting against the common enemy of COVID-19: a practice of building a community with a shared future for mankind.

The outbreak of coronavirus disease 2019 (COVID-19) has caused more than 80 813 confirmed cases in all provinces of China, and 21 110 cases reported in 93 countries of six continents as of 7 March 2020 since middle December 2019. Due to biological nature of the novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with faster spreading and unknown transmission pattern, it makes us in a difficulty position to contain the disease transmission globally. To date, we have found it is one of the greatest challenges to human beings in fighting against COVID-19 in the history, because SARS-CoV-2 is different from SARS-CoV and MERS-CoV in terms of biological features and transmissibility, and also found the containment strategies including the non-pharmaceutical public health measures implemented in China are effective and successful. In order to prevent a potential pandemic-level outbreak of COVID-19, we, as a community of shared future for mankind, recommend for all international leaders to support preparedness in low and middle income countries especially, take strong global interventions by using old approaches or new tools, mobilize global resources to equip hospital facilities and supplies to protect noisome infections and to provide personal protective tools such as facemask to general population, and quickly initiate research projects on drug and vaccine development. We also recommend for the international community to develop better coordination, cooperation, and strong solidarity in the joint efforts of fighting against COVID-19 spreading recommended by the joint mission report of the WHO-China experts, against violating the International Health Regulation (WHO, 2005), and against stigmatization, in order to eventually win the battle against our common enemy - COVID-19.

IL-17A neutralizing antibody attenuates eosinophilic meningitis caused by Angiostrongylus cantonensis by involving IL-17RA/Traf6/NF-κB signaling.

BACKGROUND: Angiostrongylus cantonensis (A. cantonensis) is a foodborne parasite that can invade the central nervous system (CNS), resulting in eosinophilic meningitis (EM). However, the mechanism by which A. cantonensis causes eosinophilic infiltration into CNS is not well understood. METHODS: In this study eosinophilic infiltration into the CNS caused by A. cantonensis was assessed based on eosinophil counts and evaluation of interleukin (IL)-5 and -13 levels by real-time PCR in brain of Balb/c mice. The expression and activation of IL-17A, IL17 receptor (IL-17R A), and IL-17RC and the related signaling molecules nuclear factor (NF)-κB1, NF-κB2, NF-κB activator (Act)1, tumor necrosis factor receptor-associated factor (Traf)5, and Traf6 during A. cantonensis infection in brain tissue of Balb/c mice were examined by real-time, western blotting and immunofluroence. A. cantonensis-infected Balb/c mice were treated with IL-17A neutralizing antibody to evaluate the role of IL17A in eosinophil accumulation in the CNS. RESULTS: Our results showed A. cantonensis infection caused eosinophil accumulation and alterations in IL-5 and -13 levels. The expression of IL-17A and -17RA, Act1, and Traf6 but not of IL-17RC and Traf5 was upregulated during infection; this was accompanied by NF-κB1 and -κB2 activation. Importantly, application of IL-17A neutralizing antibody attenuated eosinophil accumulation in CNS and reversed the changes in IL-5 and -13 expression caused by A. cantonensis infection. Additionally, IL-17RA and Traf6 levels decreased, which was accompanied by NF-κB inactivation. CONCLUSION: IL-17A plays an important role in EM caused by A. cantonensis, possibly through activation of NF-κB via the IL-17RA/Traf6 signaling pathway. These findings highlight the potential for using IL-17A neutralizing antibody as a therapeutic strategy for the treatment of EM.

Zoonotic parasites carried by invasive alien species in China.

BACKGROUND: The invasive alien species may lead to great environmental and economic crisis due to its strong capability of occupying the biological niche of native species and altering the ecosystem of the invaded area. However, its potential to serve as the vectors of some specific zoonotic pathogens, especially parasites, has been neglected. Thus, the damage that it may cause has been hugely underestimated in this aspect, which is actually an important public health problem. This paper aims to discuss the current status of zoonotic parasites carried by invasive alien species in China. MAIN BODY: This review summarizes the reported zoonotic parasites carried by invasive alien species in China based on the Database of Invasive Alien Species in China. We summarize their prevalence, threat to human health, related reported cases, and the roles of invasive alien species in the life cycle of these parasites, and the invasion history of some invasive alien species. Furthermore, we sum up the current state of prevention and control of invasive alien species in China, and discuss about the urgency and several feasible strategies for the prevention and control of these zoonoses under the background of booming international communications and inevitable globalization. CONCLUSIONS: Information of the zoonotic parasites carried by invasive alien species neither in China or worldwide, especially related case reports, is limited due to a long-time neglection and lack of monitoring. The underestimation of their damage requires more attention to the monitoring and control and compulsory measures should be taken to control the invasive alien species carrying zoonotic parasites.

Imported parasitic diseases in mainland China: current status and perspectives for better control and prevention.

BACKGROUND: The high prevalence of parasitic diseases leads to millions of deaths and disabilities each year in developing countries. China has also been greatly affected by parasitic infections, including filariasis, leishmaniasis, malaria, schistosomiasis, and soil-transmitted nematodosis. However, the situation in China improved dramatically after comprehensive parasitic disease control efforts were strengthened, leading to the elimination of filariasis in 2006 and to significant control over other diseases. However, imported parasitic disease cases are inevitable, and such cases have increasingly been reported as a result of enhanced globalization and international or regional cooperation. These imported diseases represent a major obstacle to the elimination of several parasitoses, such as malaria. MAIN TEXT: This paper reviews imported cases of parasitic diseases in mainland China, particularly malaria and schistosomiasis, based on data reported separately by the Chinese annual reports and from other published papers. We summarize the new challenges that face parasitic disease control efforts in mainland China and perspectives regarding better control. We argue that both the provision of professional education and updated training for medical care personnel and the management and surveillance of people entering China are essential. We recommend that Chinese migrant workers should be considered a priority group for health education and that public awareness of imported diseases should be emphasized. Furthermore, we underscore the importance of investigating the distribution of introduced/potential vectors, parasite susceptibility, and improvements in diagnostic techniques and drug stocks. CONCLUSIONS: Imported cases have become the main challenge to the elimination of several parasitoses, such as malaria and schistosomiasis, in mainland China. China should act to meet these challenges, which are closely associated with national biological safety.

Snail-borne parasitic diseases: an update on global epidemiological distribution, transmission interruption and control methods.

BACKGROUND: Snail-borne parasitic diseases, such as angiostrongyliasis, clonorchiasis, fascioliasis, fasciolopsiasis, opisthorchiasis, paragonimiasis and schistosomiasis, pose risks to human health and cause major socioeconomic problems in many tropical and sub-tropical countries. In this review we summarize the core roles of snails in the life cycles of the parasites they host, their clinical manifestations and disease distributions, as well as snail control methods. MAIN BODY: Snails have four roles in the life cycles of the parasites they host: as an intermediate host infected by the first-stage larvae, as the only intermediate host infected by miracidia, as the first intermediate host that ingests the parasite eggs are ingested, and as the first intermediate host penetrated by miracidia with or without the second intermediate host being an aquatic animal. Snail-borne parasitic diseases target many organs, such as the lungs, liver, biliary tract, intestines, brain and kidneys, leading to overactive immune responses, cancers, organ failure, infertility and even death. Developing countries in Africa, Asia and Latin America have the highest incidences of these diseases, while some endemic parasites have developed into worldwide epidemics through the global spread of snails. Physical, chemical and biological methods have been introduced to control the host snail populations to prevent disease. CONCLUSIONS: In this review, we summarize the roles of snails in the life cycles of the parasites they host, the worldwide distribution of parasite-transmitting snails, the epidemiology and pathogenesis of snail-transmitted parasitic diseases, and the existing snail control measures, which will contribute to further understanding the snail-parasite relationship and new strategies for controlling snail-borne parasitic diseases.

Infection by the nematode Angiostrongylus cantonensis induces differential expression of miRNAs in mouse brain.

BACKGROUND: The parasitic nematode Angiostrongylus cantonensis is the primary pathogen causing eosinophilic meningitis and meningoencephalitis in nonpermissive hosts. The larval parasites are eliminated by the host's immune responses in the central nervous system (CNS) through infiltration of eosinophils and lymphocytes. This study aimed to determine primary alterations of microRNA (miRNA) during A. cantonensis infection in mice. METHODS: miRNA array was used to analyze the expression of miRNA in uninfected and A. cantonensis-infected mouse brains at 21 days postinfection (dpi). Target genes were predicted by miRDB software, and protein-protein interaction network was analyzed using STRING v9.1. Expression levels of selected miRNAs and cytokine production were verified by quantitative reverse transcription polymerase chain reaction (qRT-PCR). RESULTS: Twenty-five mature miRNAs showed differential expression in infected mouse brains, of which 24 were upregulated and one was downregulated compared to the uninfected control. These 25 miRNAs were divided into five clusters, and the first upregulated cluster was selected for further bioinformatics analysis. Target gene prediction and gene ontology (GO) enrichment analysis revealed that the miRNAs were mainly related to the immune response. Furthermore, six target genes of mmu-miR-146a-5p were predicted to interact with tumor necrosis factor alpha (TNF-α). The in vitro study suggested that transfected mmu-miR-146a-5p inhibitor upregulated TNF-α and its target gene Traf6 in microglia following stimulation with A. cantonensis larval antigen. CONCLUSION: This study suggested a critical role of miRNAs in the host defense during A. cantonensis infection, providing new insights into the molecular mechanisms underlying the interaction between mmu-miR-146a-5p and TNF-α in angiostrongyliasis in nonpermissive hosts.

Parasitology should not be abandoned: data from outpatient parasitological testing in Guangdong, China.

Over the past six decades, the Chinese government made parasitoses with a high disease burden, including soil-transmitted nematode infections, malaria, leishmaniasis, filariasis, and schistosomiasis, a public health priority because they were seen to be crucial impediments to the development of rural areas. As a result, these debilitating parasitic diseases that used to be widely prevalent have been well controlled or eliminated. Consequently, less attention has been paid to parasitic infection during the rapid development of the economy, especially in developed areas. However, our investigations conducted in the parasitological laboratory of Sun Yat-sen University (Guangzhou, Guangdong, China) show that emerging parasitic diseases still threaten many people's health, with 340 of 880 outpatients (38.6%) receiving a diagnosis of parasitic disease, among whom 201 (59.1%) had clonorchiasis and 120 (35.3%) had taeniasis/cysticercosis. Furthermore, our doctors are not equipped with sufficient parasitology knowledge because this discipline is not able to maintain attraction. Many parasitic infections that result in severe consequences are treatable and preventable, but the phenomena of misdiagnosis and missed diagnosis are common and merit attention.

Nitric oxide blocks the development of the human parasite Schistosoma japonicum.

Human schistosomiasis, caused by Schistosoma species, is a major public health problem affecting more than 700 million people in 78 countries, with over 40 mammalian host reservoir species complicating the transmission ecosystem. The primary cause of morbidity is considered to be granulomas induced by fertilized eggs of schistosomes in the liver and intestines. Some host species, like rats (Rattus norvegicus), are naturally intolerant to Schistosoma japonicum infection, and do not produce granulomas or pose a threat to transmission, while others, like mice and hamsters, are highly susceptible. The reasons behind these differences are still a mystery. Using inducible nitric oxide synthase knockout (iNOS-/-) Sprague-Dawley rats, we found that inherent high expression levels of iNOS in wild-type (WT) rats play an important role in blocking growth, reproductive organ formation, and egg development in S. japonicum, resulting in production of nonfertilized eggs. Granuloma formation, induced by fertilized eggs in the liver, was considerably exacerbated in the iNOS-/- rats compared with the WT rats. This inhibition by nitric oxide acts by affecting mitochondrial respiration and energy production in the parasite. Our work not only elucidates the innate mechanism that blocks the development and production of fertilized eggs in S. japonicum but also offers insights into a better understanding of host-parasite interactions and drug development strategies against schistosomiasis.

Phylogeography of Angiostrongylus cantonensis (Nematoda: Angiostrongylidae) in southern China and some surrounding areas.

Angiostrongylus cantonensis is of increasing public health importance as the main zoonotic pathogen causing eosinophilic meningitis or meningoencephalitis, which has been documented all over the world. However, there are very limited studies about its phylogeography and spread pattern. In the present study, the phylogeography of A. cantonensis in southern China (including Taiwan) and partial areas of Southeast Asia were studied based on the sequences of complete mitochondrial cytochrome b (Cytb) gene. A total of 520 individuals of A. cantonensis obtained from 13 localities were sequenced for the analyses and grouped into 42 defined haplotypes. The phylogenetic tree (NJ tree and BI tree) revealed a characteristic distribution pattern of the four main lineages, with detectable geographic structure. Genetic differentiation among populations was significant, but demographic expansion could not be detected by either neutrality tests or mismatch distribution analysis, which implied a low gene flow among the local populations in different regions where the samples were collected. Two unique lineages of the A. cantonensis population in Taiwan were detected, which suggests its multiple origin in the island. Populations in Hekou (China) and Laos showed the highest genetic diversities, which were supported by both genetic diversity indices and AMOVA. These results together infer that the area around Thailand or Hekou in Yunnan province, China are the most likely origins of Angiostrongylus cantonensis.

Soluble antigens from the neurotropic pathogen Angiostrongylus cantonensis directly induce thymus atrophy in a mouse model.

The nematode Angiostrongylus cantonensis (A.C.) is a neurotropic pathogen; stage-III larva invade the human (non-permissive host) central nervous system (CNS) to cause eosinophilic meningitis or meningoencephalitis accompanied by immunosuppression. In an A.C.-infectedmouse (another non-permissive host) model, CNS damage-associated T cell immune deficiency and severe inflammation were proposed to result from activation of the hypothalamic-pituitary-adrenal (HPA) axis. However, glucocorticoids are anti-inflammatory agents. Additionally, while defects in thymic stromal/epithelial cells (TECs) are the major reason for thymic atrophy, TECs do not express the glucocorticoid receptor. Therefore, activation of the HPA axis cannot fully explain the thymic atrophy and inflammation. Using an A.C.-infected mouse model, we found that A.C.-infected mice developed severe thymic atrophy with dramatic impairments in thymocytes and TECs, particularly cortical TECs, which harbor CD4+CD8+ double-positive thymocytes. The impairments resulted from soluble antigens (sAgs) from A.C. in the thymuses of infected mice, as intrathymic injection of these sAgs into live mice and the addition of these sAgs to thymic cell culture resulted in thymic atrophy and cellular apoptosis, respectively. Therefore, in addition to an indirect effect on thymocytes through the HPA axis, our study reveals a novel mechanism by which A.C. infection in non-permissive hosts directly induces defects in both thymocytes and TECs via soluble antigens.

Diagnosis of Strongyloides stercoralis by morphological characteristics combine with molecular biological methods.

Strongyloidiasis is one of the neglected tropical diseases caused by infection with the nematode Strongyloides genus and distributed worldwide. Strongyloidiasis can be fatal in immunosuppressed patients induced hyperinfection or disseminated strongyloidiasis. Unfortunately, until now, due to the unspecific clinical symptom in infected individuals and the low sensitivity diagnosis of strongyloidiasis, many patients were misdiagnosed every year. Furthermore, the larvae of the Strongyloides stercoralis (S. stercoralis) is similar to other nematodes such as hookworm, Trichostrongylus increased the difficulty of diagnosis. In this case, the patient is a 63-year-old male person, who had a nearly 30 years medical history of asthma and emphysema, and 4-5-year medical history of diabetes. The sputum examination found some parasite larvae, then we identify the larvae using clinical observation and morphological characteristics combine with examined cytochrome oxidase subunit 1 (COX1) and 18S rRNA genes by PCR, sequence analysis and finally classified by phylogenetic analysis, the larvae were diagnosed as S. stercoralis. Our results showed that diagnosis with strongyloidiasis by morphological characteristics combine with molecular biological methods can improve the sensitive of diagnosis and provide a final diagnosis for the disease in the clinics.