Trends in parasitology最新文献

Toxoplasmosis is a common parasitic zoonosis that can be life-threatening in immunocompromised patients. About one-third of the human population is infected with Toxoplasma gondii. Primary infection triggers an innate immune response wherein IFN-γ-induced host cell GTPases, namely IRG and GBP proteins, serve as a vital component for host cell resistance. In the past decades, interest in elucidating the function of these GTPase families in controlling various intracellular pathogens has emerged. Numerous T. gondii effectors were identified to inactivate particular IRG proteins. T. gondii is re-optimizing its effectors to combat IRG function and in this way secures transmission. We discuss the IRG-specific effectors employed by the parasite in murine infections, contributing to a better understanding of T. gondii virulence.

Plant-parasitic nematodes (PPNs) are widely distributed and highly adaptable. To evade the invasion and infection of PPNs, plants initiate a series of defense responses. In turn, PPNs secrete effectors into the host tissues to suppress plant defense. In this ongoing battle between PPNs and plants, complex signal transduction processes are typically involved. This article aims to review the plant signaling network involved in host perception by the nematode, nematode perception, and downstream activation of plant defense signaling and how nematodes attempt to interfere with this network. Our goal is to establish a foundation for elucidating the signaling and regulatory mechanisms of plant-nematode interactions, and to provide insights and tools for developing PPN-resistant crops and technologies.

The development of new drug modalities has been facilitated recently by the introduction of boron as a component of organic compounds, and specifically within a benzoxaborale scaffold. This has enabled exploration of new chemical space and the development of effective compounds targeting a broad range of morbidities, including infections by protozoa, fungi, worms, and bacteria. Most notable is the recent demonstration of a single oral dose cure using acoziborole against African trypanosomiasis. Common and species-/structure-specific interactions between benzoxaboroles and parasite species have emerged and provide vital insights into the mechanisms of cidality, as well as potential challenges in terms of resistance and/or side effects. Here, we discuss the literature specific to benzoxaborole studies in parasitic protists and consider unanswered questions concerning this important new drug class.

In a tour de force, Hart and colleagues recently used a technique known as BASEHIT (bacterial selection to elucidate host-microbe interactions in high throughput) to screen a yeast display library containing 3324 curated human exoproteins with 82 pathogen samples, focusing on vector-borne pathogens, to identify 1303 putative interactions.

Although lymphatic filariasis and onchocerciasis have been targeted for global elimination, these helminth infections are still a major public health problem across the tropics and subtropics. Despite decades of research, treatment options remain limited and drugs that completely clear the infections, and can be used on a large scale, are still unavailable. In the present review we discuss the strengths and weaknesses of currently available treatments and new ones in development. Novel candidates (corallopyronin A, DNDi-6166, emodepside, and oxfendazole) are currently moving through (pre)clinical development, while the development of two candidates (AWZ1066S and ABBV-4083/flubentylosin) was recently halted. The preclinical R&D pipeline for filarial infections continues to be limited, and recent setbacks highlight the importance of continuous drug discovery and testing.

Socially living animals can counteract disease through cooperative defences, leading to social immunity that collectively exceeds the sum of individual defences. In superorganismal colonies of social insects with permanent caste separation between reproductive queen(s) and nonreproducing workers, workers are obligate altruists and thus engage in unconditional social immunity, including highly specialised and self-sacrificial hygiene behaviours. Contrastingly, cooperation is facultative in cooperatively breeding families, where all members are reproductively totipotent but offspring transiently forgo reproduction to help their parents rear more siblings. Here, helpers should either express condition-dependent social immunity or disperse to pursue independent reproduction. We advocate inclusive fitness theory as a framework to predict when and how indirect fitness gains may outweigh direct fitness costs, thus favouring conditional social immunity.

Leishmania is an intracellular protozoan transmitted by sand fly vectors; it causes cutaneous, mucocutaneous, or visceral disease. Its growth and survival are impeded by type 1 T helper cell responses, which entail interferon (IFN)-γ-mediated macrophage activation. Leishmania partially escapes this host defense by triggering immune cell and cytokine responses that favor parasite replication rather than killing. Novel methods for in situ analyses have revealed that the pathways of immune control and microbial evasion are strongly influenced by the tissue context, the micro milieu factors, and the metabolism at the site of infection, which we collectively term the 'immunomicrotope'. Understanding the components and the impact of the immunomicrotope will enable the development of novel strategies for the treatment of chronic leishmaniasis.