Fasciola hepatica is refractory to complement killing by preventing attachment of mannose binding lectin (MBL) and inhibiting MBL-associated serine proteases (MASPs) with serpins

The complement system is a first-line innate host immune defence against invading pathogens. It is activated via three pathways, termed Classical, Lectin and Alternative, which are mediated by antibodies, carbohydrate arrays or microbial liposaccharides, respectively. The three complement pathways converge in the formation of C3-convertase followed by the assembly of a lethal pore-like structure, the membrane attack complex (MAC), on the pathogen surface. We found that the infectious stage of the helminth parasite Fasciola hepatica, the newly excysted juvenile (NEJ), is resistant to the damaging effects of complement. Despite being coated with mannosylated proteins, the main initiator of the Lectin pathway, the mannose binding lectin (MBL), does not bind to the surface of live NEJ. In addition, we found that recombinantly expressed serine protease inhibitors secreted by NEJ (rFhSrp1 and rFhSrp2) selectively prevent activation of the complement via the Lectin pathway. Our experiments demonstrate that rFhSrp1 and rFhSrp2 inhibit native and recombinant MBL-associated serine proteases (MASPs), impairing the primary step that mediates C3b and C4b deposition on the NEJ surface. Indeed, immunofluorescence studies show that MBL, C3b, C4b or MAC are not deposited on the surface of NEJ incubated in normal human serum. Taken together, our findings uncover new means by which a helminth parasite prevents the activation of the Lectin complement pathway to become refractory to killing via this host response, in spite of presenting an assortment of glycans on their surface.

Differentiating Trypanosoma cruzi in a Host Mammalian Cell Imaged in Aqueous Liquid by Atmospheric Scanning Electron Microscopy

Using Atmospheric Scanning Electron Microscopy (ASEM), we visualized interaction between infectious stage of Trypanosoma cruzi and completely intact host mammalian cell. Plasma membrane appears translucent under ASEM, which not only enables direct observation of T. cruzi within its host cell, but also reveals internal structures of the parasite itself.

Efficacy of Entomopathogenic Nematodes Against Three Species of Stored Product Insects

Two specis of entomopathogenic nematodes (EPNs), Steinernema riobravi, symbolized by Sr, and Heterorabditisbacterophora, symbolized by Hb,were tested by using five concentrations: 125, 250, 500, 1000, and 2000 an infectiousphase, ml of the type Sr and four concentrations of 500, 1000, 2000 and 3000infectious phase/mlof the type Hb against Cowpea weevil, Callosobruchus maculates,Khapra beetle, Trogoderma granarium, and Rust red flour beetle Triboliumcastaneum, using three exposure times of 24, 48, and 72 h. The mortalityrate increased withincreasing in concentrations and the exposure period. The results showed that the highest mortality rate was 16.67 whole insects recorded for the 2000 infectious phase/ml with Sr nematodes after 72 hours post- treatment ofC. maculatus. The results showed that the highest rate mortality,which is 20 larvae, was recorded for the infectious phase dose of the genus nematode (Hb), all of which are 500, 1000, 2000 and 3000 gastricphase/ml, and for all exposure periods used between 24 hours and up to 72 hours against the larvae of the T. granarium. The results showed that the highest rate of mortality 10.00 whole insects was recorded for the dose of 3000 Infectious stage/ml and at the exposure time 72 hours, while the lowest rate for this mortality of 1.33 adult insects for rusty flour beetle was recorded for the dose of 500 infectious stage/ml and for the exposure time only 24 hours. The resultsindicated that mortality rate was increasing against any increase in both the exposure time and the dose of nematodes of the genus Hb.

Comparison of antigen- and RT-PCR-based testing strategies for detection of SARS-CoV-2 in two high-exposure settings

Surveillance testing for infectious disease is an important tool to combat disease transmission at the population level. During the SARS-CoV-2 pandemic, RT-PCR tests have been considered the gold standard due to their high sensitivity and specificity. However, RT-PCR tests for SARS-CoV-2 have been shown to return positive results when performed to individuals who are past the infectious stage of the disease. Meanwhile, antigen-based tests are often treated as a less accurate substitute for RT-PCR, however, new evidence suggests they may better reflect infectiousness. Consequently, the two test types may each be most optimally deployed in different settings. Here, we present an epidemiological model with surveillance testing and coordinated isolation in two congregate living settings (a nursing home and a university dormitory system) that considers test metrics with respect to viral culture, a proxy for infectiousness. Simulations show that antigen-based surveillance testing coupled with isolation greatly reduces disease burden and carries a lower economic cost than RT-PCR-based strategies. Antigen and RT-PCR tests perform different functions toward the goal of reducing infectious disease burden and should be used accordingly.

Yersinia pseudotuberculosis YopE prevents uptake by M cells and instigates M cell extrusion in human ileal enteroid-derived monolayers.

Many pathogens use M cells to access the underlying Peyers patches and spread to systemic sites via the lymph as demonstrated by ligated loop murine intestinal models. However, the study of interactions between M cells and microbial pathogens has stalled due to the lack of cell culture systems. To overcome this obstacle, we use human ileal enteroid-derived monolayers containing five intestinal cell types including M cells to study the interactions between the enteric pathogen, Yersinia pseudotuberculosis (Yptb) and M cells. The Yptb type three secretion system (T3SS) effector Yops inhibit host defenses including phagocytosis and are critical for colonization of the intestine and Peyers patches. Therefore, it is not understood how Yptb traverses through M cells to breach the epithelium. By growing Yptb under two physiological conditions that mimic the early infectious stage (low T3SS-expression) or host-adapted stage (high T3SS-expression), we found that large numbers of Yptb specifically associated with M cells, recapitulating murine studies. Transcytosis through M cells was significantly higher by Yptb expressing low levels of T3SS, because YopE and YopH prevented Yptb uptake. YopE also caused M cells to extrude from the epithelium without inducing cell-death or disrupting monolayer integrity. Sequential infection with early infectious stage Yptb reduced host-adapted Yptb association with M cells. These data underscore the strength of enteroids as a model by discovering that Yops impede M cell function, indicating that early infectious stage Yptb more effectively penetrates M cells while the host may defend against M cell penetration of host-adapted Yptb.

Comparison of antigen- and RT-PCR-based testing strategies for detection of Sars-Cov-2 in two high-exposure settings

Surveillance testing for infectious disease is an important tool to combat disease transmission at the population level. During the SARS-CoV-2 pandemic, RT-PCR tests have been considered the gold standard due to their high sensitivity and specificity. However, RT-PCR tests for SARS-CoV-2 have been shown to return positive results when administered to individuals who are past the infectious stage of the disease. Meanwhile, antigen-based tests are often treated as a less accurate substitute for RT-PCR, however, new evidence suggests they may better reflect infectiousness. Consequently, the two test types may each be most optimally deployed in different settings. Here, we present an epidemiological model with surveillance testing and coordinated isolation in two congregate living settings (a nursing home and a university dormitory system) that considers test metrics with respect to viral culture, a proxy for infectiousness. Simulations show that antigen-based surveillance testing coupled with isolation greatly reduces disease burden and carries a lower economic cost than RT-PCR-based strategies. Antigen and RT-PCR tests perform different functions toward the goal of reducing infectious disease burden and should be used accordingly.

Evolution of an asymptomatic first stage of infection in a heterogeneous population

Pathogens evolve different life-history strategies, which depend in part on differences in their host populations. A central feature of hosts is their population structure (e.g. spatial). Additionally, hosts themselves can exhibit different degrees of symptoms when newly infected; this latency is a key life-history property of pathogens. With an evolutionary-epidemiological model, we examine the role of population structure on the evolutionary dynamics of latency. We focus on specific power-law-like formulations for transmission and progression from the first infectious stage as a function of latency, assuming that the across-group to within-group transmission ratio increases if hosts are less symptomatic. We find that simple population heterogeneity can lead to local evolutionarily stable strategies (ESSs) at zero and infinite latency in situations where a unique ESS exists in the corresponding homogeneous case. Furthermore, there can exist more than one interior evolutionarily singular strategy. We find that this diversity of outcomes is due to the (possibly slight) advantage of across-group transmission for pathogens that produce fewer symptoms in a first infectious stage. Thus, our work reveals that allowing individuals without symptoms to travel can have important unintended evolutionary effects and is thus fundamentally problematic in view of the evolutionary dynamics of latency.

Pathological effects of ECHINOSTOMA PARAENSEI infection associated with pyogenic abscesses caused by PSEUDOMONAS AERUGINOSA in swiss mice

The trematode Echinostoma paraensei is an intestinal parasite transmitted by ingestion of the infectious stage of metacercariae. For scientific purposes, its life cycle has been maintained in the laboratory, allowing analysis using various biological approaches. Different parasite isolates have revealed atypical patterns of migration and establishment in ectopic sites in Swiss-Webster mice. During the investigation of the biological life cycle of an E. paraensei isolate from the silvatic rodent Nectomys squamipes collected in the municipality of Rio Bonito (State of Rio de Janeiro), a bacterial coinfection with Pseudomonas aeruginosa was observed, which produced anatomopathological alterations, mainly in the liver, bile ducts, pancreas, and small intestine. The main macroscopic signs were the whitish suppurative pyogenic punctual lesions. The histological sections stained by hematoxylin-eosin showed an intense inflammatory reaction formed by mononuclear cells and macrophages surrounding the bile ducts, although the hepatic parenchyma still presented its normal aspect. Thus, pyogenic abscesses can be associated with E. paraensei infection depending on the strain and aggravating pathogenesis in the definitive host.KEY WORDS: Liver abscess; Swiss mice; trematode infection.