Angiostrongylus cantonensis induces energy imbalance and dyskinesia in mice by reducing the expression of melanin-concentrating hormone.

BACKGROUND: Infection with Angiostrongylus cantonensis (AC) in humans or mice can lead to severe eosinophilic meningitis or encephalitis, resulting in various neurological impairments. Developing effective neuroprotective drugs to improve the quality of life in affected individuals is critical. METHODS: We conducted a Gene Ontology enrichment analysis on microarray gene expression (GSE159486) in the brains of AC-infected mice. The expression levels of melanin-concentrating hormone (MCH) were confirmed through real-time quantitative PCR (RT-qPCR) and immunofluorescence. Metabolic parameters were assessed using indirect calorimetry, and mice's energy metabolism was evaluated via pathological hematoxylin and eosin (H&E) staining, serum biochemical assays, and immunohistochemistry. Behavioral tests assessed cognitive and motor functions. Western blotting was used to measure the expression of synapse-related proteins. Mice were supplemented with MCH via nasal administration. RESULTS: Postinfection, a marked decrease in Pmch expression and the encoded MCH was observed. Infected mice exhibited significant weight loss, extensive consumption of sugar and white fat tissue, reduced movement distance, and decreased speed, compared with the control group. Notably, nasal administration of MCH countered the energy imbalance and dyskinesia caused by AC infection, enhancing survival rates. MCH treatment also increased the expression level of postsynaptic density protein 95 (PSD95) and microtubule-associated protein-2 (MAP2), as well as upregulated transcription level of B cell leukemia/lymphoma 2 (Bcl2) in the cortex. CONCLUSIONS: Our findings suggest that MCH improves dyskinesia by reducing loss of synaptic proteins, indicating its potential as a therapeutic agent for AC infection.

Diagnostic criteria and case definitions for abdominal angiostrongyliasis: a systematic review from the Brazilian experience.

Although rare, Angiostrongylus costaricensis infection may be a more prevalent etiology of inflammatory bowel disease than ulcerative colitis and Chron's disease in endemic areas in Central and South America. The present study reviewed the occurrence of A. costaricensis in Brazil, its clinical presentation and pathology; and proposed diagnostic criteria and case definitions for abdominal angiostrongyliasis (AA). Southern and southeastern Brazilian regions are the main endemic areas, and AA affects both genders and all age groups. A review of all 23 published reports of 51 Brazilian patients highlighted the following features that were subsequently classified as minor diagnostic criteria: abdominal pain, palpable mass in the right lower abdominal quadrant, history of exposure, ileocecal tumor, and intestinal perforation with wall thickening. Proposed major criteria include right lower quadrant abdominal pain, blood eosinophilia, positive serology (antibody detection), intense eosinophilic infiltration that involves all strata of the intestinal wall, eosinophilic granulomatous reaction, and eosinophilic vasculitis. In addition to the definitions of suspected and possible cases according to increasing strength of evidence of this infection, demonstration of worms/eggs/larvae in tissues or Angiostrongylus DNA in tissues or serum are required for a confirmed diagnosis. The application of the proposed criteria and definitions may improve patient management, epidemiologic surveillance, and identification of new endemic areas.

Angiostrongylus dujardini infection in a coconut lorikeet (Trichoglossus haematodus) from a zoological garden in Switzerland.

Angiostrongylus spp. (Metastrongyloidea) can cause severe disease in several animal species and humans. This report describes an infection with Angiostrongylus dujardini in a captive coconut lorikeet (Trichoglossus haematodus) from a zoo in Switzerland. The bird was reported being attacked by conspecifics, removed from the flock, and hospitalized. It showed lethargy, moderately reduced body condition, and lack of reaction to visual stimuli. Analgesic and antibiotic treatment were initiated but because of worsening of its general condition, the bird was euthanized the following day. Necropsy revealed multifocal, subcutaneous hemorrhages, diffusely reddened lungs and a moderately dilated right heart with several intraluminal nematodes embedded in a coagulum. Four worms were collected and microscopically examined. They were identified as adult females, measuring 19-21 mm long x 0.4-0.5 mm wide, with general morphological and morphometric characteristics consistent with angiostrongylid nematodes. In lung sections, multifocal collection of thin-walled embryonated eggs in variable stages of development was observed along with fully developed nematode larvae within the lumina of alveoli and lung vessels. Associated granulomatous infiltrates indicated a severe, multifocal, chronic, granulomatous pneumonia. The diagnosis of A. dujardini infection was formulated by morphological examination of adult and larval stages, supported by molecular analysis (PCR-amplification and sequencing of the ITS2, 5.8S and 28S rDNA flanking regions). This is the first report of A. dujardini infection in an avian species, providing evidence that birds can serve as accidental hosts of this parasite in addition to mammals, and that the parasite can reach maturity and multiply in the avian cardiorespiratory system.

Th2-dependent STAT6-regulated genes in intestinal epithelial cells mediate larval trapping during secondary Heligmosomoides polygyrus bakeri infection.

Gastrointestinal helminths are a major health threat worldwide. Alternatively activated macrophages (AAMs) have been shown to contribute to host protection during secondary helminth infections. AAMs express effector molecules that depend on activation of the IL-4- or IL-13-induced transcription factor signal transducer and activator of transcription 6 (STAT6). However, the specific role of STAT6-regulated genes like Arginase-1 (Arg1) from AAMs or STAT6-regulated genes in other cell types for host protection remains unclear. To address this point, we generated mice expressing STAT6 only in macrophages (Mac-STAT6 mouse). In the model of Heligmosomoides polygyrus bakeri (Hpb) infection, Mac-STAT6 mice could not trap larvae in the submucosa of the small intestine after secondary infection. Further, mice lacking Arg1 in hematopoietic and endothelial cells were still protected from secondary Hpb infection. On the other hand, specific deletion of IL-4/IL-13 in T cells blunted AAM polarization, activation of intestinal epithelial cells (IECs) and protective immunity. Deletion of IL-4Rα on IEC also caused loss of larval trapping while AAM polarization remained intact. These results show that Th2-dependent and STAT6-regulated genes in IECs are required and AAMs are not sufficient for protection against secondary Hpb infection by mechanisms that remain to be investigated.

A practical guide for the diagnosis of abdominal angiostrongyliasis caused by the nematode Angiostrongylus costaricensis.

Abdominal angiostrongyliasis (AA) is a severe parasitic infection caused by the nematode Angiostrongylus costaricensis. This disease is characterized by abdominal pain, a strong inflammatory eosinophilic response in the blood and tissues, and eventually intestinal perforation. Diagnosis of AA is challenging since there are no commercially available serological kits for A. costaricensis, and thus, histopathological analysis remains the gold standard. Herein we provide a decision flowchart for clinicians to improve the diagnosis of AA based on a patient's clinical manifestations, laboratory findings, macroscopic observations of the gut lesions, as well as characteristic microscopic alterations in biopsies. A brief discussion of the available polymerase chain reaction and in-house serological methods is also presented. The aim of this mini-review is to improve the diagnosis of AA, which should lead to prompt detection of cases and better estimates of the epidemiology and geographical distribution of A. costaricensis.

IL-4 and helminth infection downregulate MINCLE-dependent macrophage response to mycobacteria and Th17 adjuvanticity.

The myeloid C-type lectin receptor (CLR) MINCLE senses the mycobacterial cell wall component trehalose-6,6'-dimycolate (TDM). Recently, we found that IL-4 downregulates MINCLE expression in macrophages. IL-4 is a hallmark cytokine in helminth infections, which appear to increase the risk for mycobacterial infection and active tuberculosis. Here, we investigated functional consequences of IL-4 and helminth infection on MINCLE-driven macrophage activation and Th1/Th17 adjuvanticity. IL-4 inhibited MINCLE and cytokine induction after macrophage infection with Mycobacterium bovis bacille Calmette-Guerin (BCG). Infection of mice with BCG upregulated MINCLE on myeloid cells, which was inhibited by IL-4 plasmid injection and by infection with the nematode Nippostrongylus brasiliensis in monocytes. To determine the impact of helminth infection on MINCLE-dependent immune responses, we vaccinated mice with a recombinant protein together with the MINCLE ligand trehalose-6,6-dibehenate (TDB) as adjuvant. Concurrent infection with N. brasiliensis or with Schistosoma mansoni promoted T cell-derived IL-4 production and suppressed Th1/Th17 differentiation in the spleen. In contrast, helminth infection did not reduce Th1/Th17 induction by TDB in draining peripheral lymph nodes, where IL-4 levels were unaltered. Upon use of the TLR4-dependent adjuvant G3D6A, N. brasiliensis infection impaired selectively the induction of splenic antigen-specific Th1 but not of Th17 cells. Inhibition of MINCLE-dependent Th1/Th17 responses in mice infected with N. brasiliensis was dependent on IL-4/IL-13. Thus, helminth infection attenuated the Th17 response to MINCLE-dependent immunization in an organ- and adjuvant-specific manner via the Th2 cytokines IL-4/IL-13. Taken together, our results demonstrate downregulation of MINCLE expression on monocytes and macrophages by IL-4 as a possible mechanism of thwarted Th17 vaccination responses by underlying helminth infection.

Relationship between histopathological lesions and oxidative stress in mice infected with Angiostrongylus costaricensis.

This study describes changes in oxidative stress (OS) parameters in mice experimentally infected with Angiostrongylus costaricensis, which causes abdominal angiostrongyliasis. For this, 28 Swiss mice were used, divided into two groups (G1 and G2), with 14 animals each. Of these, eight were infected with ten infective larvae each, by gavage, and six were used as a control group. Mice from G1 and G2 were euthanized at 14 days and 24 days post-infection, respectively. Tissue samples were used for histopathological analysis and blood (serum) samples were taken to assess the levels of proteins, non-protein thiols (NPTs) and nitric oxide (NO), from centrifugation and subsequent collection of aliquots of the supernatant. Among OS parameters, infected mice in both groups had higher NO levels than the control group, due to the presence of: eosinophil infiltrate in the liver and intestine; pancreatitis; and intestinal granuloma. However, the infected mice of both groups showed a reduction in the levels of NPTs, in relation to the control group, due to the presence of: eosinophilic infiltrate in the liver and intestine; and intestinal granuloma. Our results suggest that A. costaricensis infection has important effects on the intestine, liver and pancreas, and the analyses were performed from the tissue of these organs. The mechanisms for these changes are related to the decrease in the body's main antioxidant defences, as demonstrated by the reduction of NPTs, thus contributing to the development of more severe tissue damage. Thus, the objective of the present study was to evaluate the relationship between histopathological lesions and markers for OS.

Parasitism in Rattus rattus and sympatric Achatina fulica by Angiostrongylus cantonensis in an urban park in southeast Brazil.

In this study, rodents (Rattus rattus) and mollusks (Achatina fulica) were captured in a small forest located in a large metropolitan city in Brazil, and they were examined to investigate possible parasitism by Angiostrongylus cantonensis. The parasites were recovered as helminths from the pulmonary arteries of the synanthropic rodents and as third-stage larvae (with Metastrongylidae family characteristics) from the mollusks. To confirm the species, these larvae were used to experimentally infect Rattus norvegicus for the posterior recovery of adult helminths. To identify the adult helminths, morphological, morphometric, molecular, and phylogenetic techniques were employed. Furthermore, we also characterized the histological lesions associated with parasitism in naturally infected definitive hosts. Our results demonstrated the occurrence of a natural life cycle of A. cantonensis (with the presence of adult helminths) in definitive hosts, Rattus rattus, and third-stage larvae in an intermediate host, A. fulica. In free-living rodents, lesions of granulomatous pneumonia in the lungs and meningitis in the brain were also found. These results warn of the risk of accidental transmission of A. cantonensis to human residents around the park because of the extensive interaction among the fauna of the park, domestic animals, and the surrounding human population.

Stat3/IL-6 signaling mediates sustained pneumonia induced by Agiostrongylus cantonensis.

Angiostrongylus cantonensis (AC) is well-documented that parasitizes the host brain and causes eosinophilic meningitis. The migration route of AC in permissive hosts is well demonstrated, while in nonpermissive hosts, it remains to be fully defined. In the present study, we exploited live imaging technology, morphological and pathological configuration analysis, and molecular biological technologies to explore the migration route of AC and the accompanying tissue damage in nonpermissive and permissive hosts. Our data indicated that, in nonpermissive host mouse, AC larvae migrated from intestinal wall to liver at 2 hours post-infection (hpi), from liver to lung at 4 hpi and then from lung to brain at 8 hpi. AC larval migration caused fatal lung injury (pneumonia) during acute and early infection phases, along with significant activation of Stat3/IL-6 signaling. In addition, AC induce sustained interstitial pneumonia in mouse and rat and pulmonary fibrosis only in rat during late infection phase. Moreover, during the early and late infection phases, Th2 cytokine expression and Stat3 and IL-6 signaling were persistently enhanced and myeloid macrophage cells were notably enriched in host lung, and administration of Stat3 and IL-6 inhibitors (C188-9 and LMT-28) attenuated AC infection-induced acute pneumonia in mice. Overall, we are the first to provide direct and systemic laboratory evidence of AC migration route in a nonpermissive host and report that infection with a high dose of AC larvae could result in acute and fatal pneumonia through Stat3/IL-6 signaling in mice. These findings may present a feasible to rational strategy to minimize the pathogenesis induced by AC.

Helminth resistance is mediated by differential activation of recruited monocyte-derived alveolar macrophages and arginine depletion.

Macrophages are known to mediate anti-helminth responses, but it remains uncertain which subsets are involved or how macrophages actually kill helminths. Here, we show rapid monocyte recruitment to the lung after infection with the nematode parasite Nippostrongylus brasiliensis. In this inflamed tissue microenvironment, these monocytes differentiate into an alveolar macrophage (AM)-like phenotype, expressing both SiglecF and CD11c, surround invading parasitic larvae, and preferentially kill parasites in vitro. Monocyte-derived AMs (Mo-AMs) express type 2-associated markers and show a distinct remodeling of the chromatin landscape relative to tissue-derived AMs (TD-AMs). In particular, they express high amounts of arginase-1 (Arg1), which we demonstrate mediates helminth killing through L-arginine depletion. These studies indicate that recruited monocytes are selectively programmed in the pulmonary environment to express AM markers and an anti-helminth phenotype.

Loss of protein tyrosine phosphatase non-receptor type 2 reduces IL-4-driven alternative macrophage activation.

Macrophages are a heterogeneous population of innate immune cells that are often divided into two major subsets: classically activated, typically pro-inflammatory (M1) macrophages that mediate host defense, and alternatively activated, tolerance-inducing (M2) macrophages that exert homeostatic and tissue-regenerative functions. Disturbed macrophage function/differentiation results either in inadequate, excessive immune activation or in a failure to induce efficient protective immune responses against pathogens. Loss-of-function variants in protein tyrosine phosphatase non-receptor type 2 (PTPN2) are associated with chronic inflammatory disorders, but the effect of macrophage-intrinsic PTPN2 loss is still poorly understood. Here we report that PTPN2-deficient macrophages fail to acquire an alternatively activated/M2 phenotype. This was the consequence of reduced IL-6 receptor expression and a failure to induce IL-4 receptor in response to IL-6, resulting in an inability to respond to the key M2-inducing cytokine IL-4. Ultimately, failure to adequately respond to IL-6 and IL-4 resulted in increased levels of M1 macrophage marker expression in vitro and exacerbated lung inflammation upon infection with Nippostrongylus brasiliensis in vivo. These results demonstrate that PTPN2 loss interferes with the ability of macrophages to adequately respond to inflammatory stimuli and might explain the increased susceptibility of PTPN2 loss-of-function carriers to developing inflammatory diseases.

Intestinal epithelial tuft cell induction is negated by a murine helminth and its secreted products.

Helminth parasites are adept manipulators of the immune system, using multiple strategies to evade the host type 2 response. In the intestinal niche, the epithelium is crucial for initiating type 2 immunity via tuft cells, which together with goblet cells expand dramatically in response to the type 2 cytokines IL-4 and IL-13. However, it is not known whether helminths modulate these epithelial cell populations. In vitro, using small intestinal organoids, we found that excretory/secretory products (HpES) from Heligmosomoides polygyrus blocked the effects of IL-4/13, inhibiting tuft and goblet cell gene expression and expansion, and inducing spheroid growth characteristic of fetal epithelium and homeostatic repair. Similar outcomes were seen in organoids exposed to parasite larvae. In vivo, H. polygyrus infection inhibited tuft cell responses to heterologous Nippostrongylus brasiliensis infection or succinate, and HpES also reduced succinate-stimulated tuft cell expansion. Our results demonstrate that helminth parasites reshape their intestinal environment in a novel strategy for undermining the host protective response.

TNF-α Triggers RIP1/FADD/Caspase-8-Mediated Apoptosis of Astrocytes and RIP3/MLKL-Mediated Necroptosis of Neurons Induced by Angiostrongylus cantonensis Infection.

Angiostrongylus cantonensis (AC) can cause severe eosinophilic meningitis or encephalitis in non-permissive hosts accompanied by apoptosis and necroptosis of brain cells. However, the explicit underlying molecular basis of apoptosis and necroptosis upon AC infection has not yet been elucidated. To determine the specific pathways of apoptosis and necroptosis upon AC infection, gene set enrichment analysis (GSEA) and protein-protein interaction (PPI) analysis for gene expression microarray (accession number: GSE159486) of mouse brain infected by AC revealed that TNF-α likely played a central role in the apoptosis and necroptosis in the context of AC infection, which was further confirmed via an in vivo rescue assay after treating with TNF-α inhibitor. The signalling axes involved in apoptosis and necroptosis were investigated via immunoprecipitation and immunoblotting. Immunofluorescence was used to identify the specific cells that underwent apoptosis or necroptosis. The results showed that TNF-α induced apoptosis of astrocytes through the RIP1/FADD/Caspase-8 axis and induced necroptosis of neurons by the RIP3/MLKL signalling pathway. In addition, in vitro assay revealed that TNF-α secretion by microglia increased upon LSA stimulation and caused necroptosis of neurons. The present study provided the first evidence that TNF-α was secreted by microglia stimulated by AC infection, which caused cell death via parallel pathways of astrocyte apoptosis (mediated by the RIP1/FADD/caspase-8 axis) and neuron necroptosis (driven by the RIP3/MLKL complex). Our research comprehensively elucidated the mechanism of cell death after AC infection and provided new insight into targeting TNF-α signalling as a therapeutic strategy for CNS injury.

Heme oxygenase-1 modulates brain inflammation and apoptosis in mice with angiostrongyliasis.

The rat nematode lungworm Angiostrongylus cantonensis undergoes obligatory intracerebral migration in its hosts and causes eosinophilic meningitis or meningoencephalitis. Heme oxygenase 1 (HO-1) has several cytoprotective properties such as anti-oxidative, anti-inflammatory, and anti-apoptotic effects. HO-1 in brain tissues was induced in A. cantonensis-infected group and showed positive modulation in cobalt protoporphyrin (CoPP)-treated groups. Assay methods for the therapeutic effect include western blot analysis, enzyme-linked immunosorbent assay, gelatin zymography, blood-brain barrier permeability evaluation and eosinophil count in cerebrospinal fluid. The combination of albendazole (ABZ) and CoPP significantly decreased pro-inflammatory cytokines, tumor necrosis factor-α, interleukin (IL)-1ß, IL-5, and IL-33 but significantly increased anti-inflammatory cytokines IL-10 and transforming growth factor-ß. In addition, worm recovery, matrix metalloproteinase-9, BBB permeability, and eosinophil counts were decreased in the ABZ and CoPP co-treated groups. Induction of HO-1 with CoPP strongly inhibited the protein levels of caspase-3 and increased the induction of annexin-V and B-cell leukemia 2. Thus, co-treatment with ABZ and CoPP prevented A. cantonensis-induced eosinophilic meningoencephalitis and its anti-apoptotic effect by promoting HO-1 signaling prior to BBB dysfunction. HO-1 induction might be a therapeutic modality for eosinophilic meningoencephalitis.

The phytonutrient cinnamaldehyde limits intestinal inflammation and enteric parasite infection.

Phytonutrients such as cinnamaldehyde (CA) have been studied for their effects on metabolic diseases, but their influence on mucosal inflammation and immunity to enteric infection are not well documented. Here, we show that consumption of CA in mice significantly down-regulates transcriptional pathways connected to inflammation in the small intestine, and alters T-cell populations in mesenteric lymph nodes. During infection with the enteric helminth Heligomosomoides polygyrus, CA treatment attenuated infection-induced changes in biological pathways connected to cell cycle and mitotic activity, and tended to reduce worm burdens. Mechanistically, CA did not appear to exert activity through a prebiotic effect, as CA treatment did not significantly change the composition of the gut microbiota. Instead, in vitro experiments showed that CA directly induced xenobiotic metabolizing pathways in intestinal epithelial cells and suppressed endotoxin-induced inflammatory responses in macrophages. Collectively, our results show that CA down-regulates inflammatory pathways in the intestinal mucosa and can limit the pathological response to enteric infection. These properties appear to be largely independent of the gut microbiota, and instead connected to the ability of CA to induce antioxidant pathways in intestinal cells. Our results encourage further investigation into the use of CA and related phytonutrients as functional food components to promote intestinal health in humans and animals.

First Case of Subretinal Ocular Angiostrongyliasis Associated with Retinal Detachment in the United States.

Angiostrongylus cantonensis, commonly known as the rat lungworm, is mostly found in Asia, the Pacific Basin, and the Caribbean, but is also endemic in Hawai'i, especially on the Island of Hawai'i. Ocular angiostrongyliasis is an uncommon but previously reported complication associated with permanent vision loss. This is the first reported case of ocular angiostrongyliasis involving the retina or posterior segment of the eye in the US. A 24-year-old male from Chicago visited the Island of Hawai'i, where he worked on a farm and ate a vegetarian diet. When he returned to Chicago, he became sick and was hospitalized for eosinophilic meningitis. One month later, he developed a retinal detachment which required surgical repair involving a pars plana vitrectomy. During the reattachment of the retina during surgery, a live motile was identified nematode in the subretinal space. An endolaser probe immobilized and killed the nematode, and it was subsequently extracted through the sclerotomy. Thermal scars around all retinal holes including the retinotomy site were made to stabilize the retina, and perfluoropropane gas was injected to achieve temporary tamponade. Thereafter, the patient's cerebrospinal fluid returned positive for angiostrongylus cantonensis antibodies. During extended follow-up, the patient eventually lost all vision in the affected eye due to recurrent retinal detachment. This case of ocular angiostrongyliasis demonstrates the importance of obtaining travel history from endemic areas, knowing the risk of developing eosinophilic meningitis, and understanding the risk of permanent vision loss in cases involving the retina.

Regulation of intestinal immunity and tissue repair by enteric glia.

Tissue maintenance and repair depend on the integrated activity of multiple cell types1. Whereas the contributions of epithelial2,3, immune4,5 and stromal cells6,7 in intestinal tissue integrity are well understood, the role of intrinsic neuroglia networks remains largely unknown. Here we uncover important roles of enteric glial cells (EGCs) in intestinal homeostasis, immunity and tissue repair. We demonstrate that infection of mice with Heligmosomoides polygyrus leads to enteric gliosis and the upregulation of an interferon gamma (IFNγ) gene signature. IFNγ-dependent gene modules were also induced in EGCs from patients with inflammatory bowel disease8. Single-cell transcriptomics analysis of the tunica muscularis showed that glia-specific abrogation of IFNγ signalling leads to tissue-wide activation of pro-inflammatory transcriptional programs. Furthermore, disruption of the IFNγ-EGC signalling axis enhanced the inflammatory and granulomatous response of the tunica muscularis to helminths. Mechanistically, we show that the upregulation of Cxcl10 is an early immediate response of EGCs to IFNγ signalling and provide evidence that this chemokine and the downstream amplification of IFNγ signalling in the tunica muscularis are required for a measured inflammatory response to helminths and resolution of the granulomatous pathology. Our study demonstrates that IFNγ signalling in enteric glia is central to intestinal homeostasis and reveals critical roles of the IFNγ-EGC-CXCL10 axis in immune response and tissue repair after infectious challenge.

SREBP1-induced fatty acid synthesis depletes macrophages antioxidant defences to promote their alternative activation.

Macrophages exhibit a spectrum of activation states ranging from classical to alternative activation1. Alternatively, activated macrophages are involved in diverse pathophysiological processes such as confining tissue parasites2, improving insulin sensitivity3 or promoting an immune-tolerant microenvironment that facilitates tumour growth and metastasis4. Recently, the metabolic regulation of macrophage function has come into focus as both the classical and alternative activation programmes require specific regulated metabolic reprogramming5. While most of the studies regarding immunometabolism have focussed on the catabolic pathways activated to provide energy, little is known about the anabolic pathways mediating macrophage alternative activation. In this study, we show that the anabolic transcription factor sterol regulatory element binding protein 1 (SREBP1) is activated in response to the canonical T helper 2 cell cytokine interleukin-4 to trigger the de novo lipogenesis (DNL) programme, as a necessary step for macrophage alternative activation. Mechanistically, DNL consumes NADPH, partitioning it away from cellular antioxidant defences and raising reactive oxygen species levels. Reactive oxygen species serves as a second messenger, signalling sufficient DNL, and promoting macrophage alternative activation. The pathophysiological relevance of this mechanism is validated by showing that SREBP1/DNL is essential for macrophage alternative activation in vivo in a helminth infection model.

Leukogram and cortisol parameters in Swiss mice experimentally infected with Angiostrongylus costaricensis.

This study describes changes in haematological parameters, cytokine profile, histopathology and cortisol levels in Swiss mice experimentally infected with Angiostrongylus costaricensis. Twenty-eight Swiss mice were divided into two groups (G1 and G2) of 14 animals each. In each group, eight animals were infected orally with ten third-stage larvae of A. costaricensis and six were used as a control group. The mice of groups G1 and G2 were sacrificed 14 and 24 days after infection, respectively. Samples were collected for histopathological and haematological analyses and determination of the cytokine profile and cortisol levels. Granulomatous reaction, eosinophilic infiltrate and vasculitis in the intestinal tract, pancreas, liver and spleen were observed with varying intensity in infected animals. Our results showed that the mice developed normocytic and hypochromic anaemia, and that the histopathological lesions caused by the experimental infection influenced increases in cortisol, neutrophil and monocyte levels. In addition to this, we detected increased interleukin-6 and tumour necrosis factor alpha levels in the infected animals.