Anaplasma phagocytophilum: deceptively simple or simply deceptive?

Anaplasma phagocytophilum is an obligate intracellular rickettsial pathogen transmitted by ixodid ticks. This bacterium colonizes myeloid and nonmyeloid cells and causes human granulocytic anaplasmosis--an important immunopathological vector-borne disease in the USA, Europe and Asia. Recent studies uncovered novel insights into the mechanisms of A. phagocytophilum pathogenesis and immunity. Here, we provide an overview of the underlying events by which the immune system responds to A. phagocytophilum infection, how this pathogen counteracts host immunity and the contribution of the tick vector for microbial transmission. We also discuss current scientific gaps in the knowledge of A. phagocytophilum biology for the purpose of exchanging research perspectives.     

Localized cellular responses to Ichthyophthirius multifiliis: protection or pathogenesis?

The ciliate Ichthyophthirius multifiliis is an economically important parasite in aquaculture as well as in the ornamental fish trade. The parasite has been well studied and details of life cycle, host response and pathogenesis have been characterized. Parasite development within host epithelial tissues initiates localized leukocytic infiltrations, although the relationship between these responses and host resistance is uncertain, and whether or not leukocyte responses play a role in protective immunity is unclear. Here Frank Cross outlines the character of localized cellular responses during I. multifiliis infection and discusses the contribution of such responses to protective immunity and pathogenesis.     

The HIV-1 accessory gene vpr can inhibit antigen-specific immune function

The 14-kDa HIV-1 accessory gene vpr has been reported to have effects on host cell biology. These activities include inhibition of cell proliferation, inhibition of NF-kappaB activation, inhibition of CD4 T-cell proliferation, and induction of apoptosis in tissue culture. This collection of activities could, in theory, impact host cell immune responses. We tested the activity of recombinant Vpr protein to inhibit T-cell activation in vitro. Here, we present data illustrating that the Vpr protein can significantly suppress T-cell activation-related cytokine elaboration and proliferation. In vivo, we observed that covaccination with plasmids expressing the vpr gene product profoundly reduces antigen-specific CD8-mediated cytotoxic T lymphocyte (CTL) activity. This supports that vpr might compromise T-cell immunity in vivo during infection. To study this aspect of Vpr biology, we developed an Adenoviral Vpr expression vector for delivery of Vpr to immune cells and to study Vpr function in the absence of other lentiviral gene products. This vector delivers a functional Vpr protein to immune cells including antigen-presenting cells (APCs). We observe that the Adeno-Vpr vector suppresses human CD4 T-cell proliferation driven by immune activation in vitro. Further study of the biology of Vpr will likely have importance for a clearer understanding of host pathogenesis as well as have important implications for HIV vaccine development.     

念珠菌性外阴阴道炎发病机制研究进展

念珠菌性外阴阴道炎是一种常见的妇女感染性疾病,该病发病机制尚未完全明确,其发病与多种因素有关,但主要归因于致病菌与宿主两方面因素。近20a的动物及临床研究显示适应性免疫涉及的几种免疫调节机制可能不是主要的保护性机制,天然免疫被认为是黏膜念珠菌感染的主要宿主防御机制;而念珠菌毒力因子的变化对于该病的发生也有重要作用。     

Plant-bacterial pathogen interactions mediated by type III effectors

Effectors secreted by the bacterial type III system play a central role in the interaction between Gram-negative bacterial pathogens and their host plants. Recent advances in the effector studies have helped cementing several key concepts concerning bacterial pathogenesis, plant immunity, and plant-pathogen co-evolution. Type III effectors use a variety of biochemical mechanisms to target specific host proteins or DNA for pathogenesis. The identifications of their host targets led to the identification of novel components of plant innate immune system. Key modules of plant immune signaling pathways such as immune receptor complexes and MAPK cascades have emerged as a major battle ground for host-pathogen adaptation. These modules are attacked by multiple type III effectors, and some components of these modules have evolved to actively sense the effectors and trigger immunity.     

Cross-talk between virus and host innate immunity in pediatric HIV-1 infection and disease progression

Variability in the susceptibility to HIV-1 infection and disease progression depends on both virus and host determinants. Some exposed individuals remain HIV-1-uninfected and HIV-1-infected subjects develop disease at varying intervals with a small percentage remaining long-term non-progressors. As innate immunity is the earliest response to microbial entry and injury, host factors that impact innate immunity may play a role in viral infectivity and pathogenesis. In the pediatric population the interactions between the virus and the host may be of particular relevance due to the still developing adaptive immune system. Data indicate that genetic variants of defensins and Toll-Like Receptors (TLRs), key elements of innate immunity, play a role in mother-to-child transmission (MTCT) of HIV-1, and in the outcome of pediatric HIV-1 disease. Although the mechanisms by which these genetic variants influence HIV-1 interactions with the host are still largely unknown, defensins and TLRs, along with their link with regulatory T cells (Tregs), may play a critical role in the onset and persistence of immune activation, a hallmark of HIV-1 disease.     

Immunity to intracellular pathogens as a complex genetic trait

Although the role of host heredity in susceptibility to infectious diseases is significant, the genetic control of immunity to infection remains poorly understood. Advances in experimental and epidemiological analyses of complex genetic traits have led to the discoveries of novel genetic determinants of host resistance. New loci that control susceptibility to a number of intracellular pathogens have been identified using mouse models of infectious diseases. The contributions of individual loci, however, vary in quantitative and qualitative manner, depending on mechanisms of pathogen virulence and genetic background of the host. In this review, we discuss how genetic analysis of host resistance contributes to further understanding of host immunity and pathogenesis of intracellular infections.     

Effects of ultraviolet B irradiation on cutaneous leishmaniasis

Protection against many infectious diseases is mediated by cellular immunity in the competent host. Ultraviolet (UV) radiation, a component of sunlight, is a potent suppressor of cell-mediated immune responses. Suzanne Holmes Giannini discusses the possible relevance of ambient levels of UVB to pathogenesis and immunity in infectious diseases, with special reference to cutaneous leishmaniasis.     

The long strange trip of Borrelia burgdorferi outer-surface protein C

Borrelia burgdorferi must adapt physiologically to two markedly different host milieus and efficiently transit between its mammalian host and arthropod vector during tick feeding. Differential production of lipoproteins is essential for spirochaetes to survive, multiply and migrate within both hosts. Outer-surface protein C (OspC), which is induced during the blood meal, is critical for transmission of Lyme disease spirochaetes by nymphal ticks. Its biological function is poorly understood, however, despite the fact that its crystal structure has been solved. Evidence has accumulated that OspC blocks clearance of spirochaetes following inoculation in skin, and it is thought to do so by facilitating evasion of innate immunity. The study by Liang and co-workers in this edition of Molecular Microbiology extends this work by showing that OspC prevents early elimination and promotes dissemination. Surprisingly, they also show that unrelated borrelial outer-surface lipoproteins can replace these functions in an ospC mutant. They propose that an abundance of lipoprotein(s) is needed to stabilize the borrelial outer membrane against innate defences. This provocative work clearly runs counter to prevailing orthodoxies of bacterial pathogenesis. It also points the way towards future studies that will clarify the 'partially specific' roles of this enigmatic molecule in Lyme disease pathogenesis.     

Salmonella typhimurium outer membrane remodeling: role in resistance to host innate immunity.

Resistance to innate immunity is essential for salmonellae pathogenesis. The salmonellae PhoP/PhoQ regulators sense host environments to promote remodeling of the bacterial envelope. This remodeling includes enzymes that modify lipopolysaccharide (LPS). Modified LPS promotes bacterial survival by increasing resistance to cationic antimicrobial peptides and by altered host recognition of LPS.     

The role of the unfolded protein response in dengue virus pathogenesis

Symptomatic dengue virus (DENV) infections range from mild fever to severe haemorrhagic disease and death. Host‐viral interactions play a significant role in deciding the fate of the infection. The unfolded protein response (UPR) is a prosurvival cellular reaction induced in response to DENV‐mediated endoplasmic reticulum stress. The UPR has complex interactions with the cellular autophagy machinery, apoptosis, and innate immunity. DENV has evolved to manipulate the UPR to facilitate its replication and to evade host immunity. Our knowledge of this intertwined network of events is continuously developing. A better understanding of the UPR mediated antiviral and proviral effects will shed light on dengue disease pathogenesis and may help development of anti‐DENV therapeutics. This review summarizes the role of the UPR in viral replication, autophagy, and DENV‐induced inflammation to describe how a host response contributes to DENV pathogenesis.     

Bacterial membrane vesicles: Biogenesis,immune regulation and pathogenesis

Outer membrane vesicles were first described approximately 50 years ago and for many years were considered to be an artifact of bacterial growth. Since that initial discovery, it has become evident that outer membrane vesicles are produced by almost all Gram‐negative bacteria as part of their normal growth in addition to driving pathogenesis within the host. More recently, the identification of membrane vesicle (MV) production by some Gram‐positive bacteria, parasites, fungi, mycobacteria and infected host cells has significantly broadened the field of MV research and emphasized their importance to pathogenesis. In this review, we will focus on discussing recent advances in the field of bacterial MV biogenesis and the mechanisms whereby they modulate immunity and contribute to pathogenesis. We will highlight findings identifying the contribution of extracellular vesicles produced by Gram‐positive bacteria, fungi, parasites, and infected host cells in mediating pathogenesis in addition to the functions of MVs produced by commensal bacteria. Finally, we will discuss recent progress in the development of bacterial MVs as novel vaccines capable of mediating cellular and humoral immune responses.     

Mammalian apoptotic signalling pathways: multiple targets of protozoan parasites to activate or deactivate host cell death

Programmed cell death is an essential mechanism of the host to combat infectious agents and to regulate immunity during infection. Consequently, activation and deactivation of the hosts' cell death pathways by protozoan parasites play critical roles in parasite control, pathogenesis, immune evasion and parasite dissemination within the host. Here, we discuss advances in the understanding of these fascinating host-parasite interactions with special emphasis on how protozoa can modulate the cell death apparatus of its host.     

Viral-mediated activation and inhibition of programmed cell death

Viruses are ubiquitous intracellular genetic parasites that heavily rely on the infected cell to complete their replication life cycle. This dependency on the host machinery forces viruses to modulate a variety of cellular processes including cell survival and cell death. Viruses are known to activate and block almost all types of programmed cell death (PCD) known so far. Modulating PCD in infected hosts has a variety of direct and indirect effects on viral pathogenesis and antiviral immunity. The mechanisms leading to apoptosis following virus infection is widely studied, but several modalities of PCD, including necroptosis, pyroptosis, ferroptosis, and paraptosis, are relatively understudied. In this review, we cover the mechanisms by which viruses activate and inhibit PCDs and suggest perspectives on how these affect viral pathogenesis and immunity.     

Designing blood-stage vaccines against Babesia bovis and B. bigemina.

The tick-transmitted apicomplexan parasites Babesia bovis and B. bigemina cause significant disease in cattle in many tropical and temperate areas of the world. These parasites present a challenge for vaccine development, and yet provide a system for studying the pathogenesis, mechanisms of protective immunity and regulation of host immune responses associated with intraerythrocytic protozoan parasites in a non-rodent species. In this article, Wendy Brown and Guy Palmer review strategies for identifying candidate vaccine antigens of B. bovis and B. bigemina and for priming immune responses to evoke strain crossprotective immunity.     

肠道微生物群落与炎症性肠病关系研究进展

目的炎症性肠病（IBD）包括克罗恩病（CD）和溃疡性结肠炎（UC）,以持续性肠道非特异性炎症为特征,通常反复发作、迁延不愈,临床上仍无特效性的治疗手段。IBD确切的发病机制尚不清楚,涉及免疫、环境及遗传等因素,这些因素共同诱导肠道炎症、黏膜损伤和修复。肠道微生物群落及其代谢产物、宿主基因易感性及肠道黏膜免疫三方面共同参与了IBD的发病机制。本文从消化道微生态角度出发,对目前IBD相关的肠道微生物群落研究现状、宿主-微生物间免疫应答及益生菌治疗等内容进行探讨。     

Towards a vaccine for Cryptococcus neoformans: principles and caveats

In the Damage-response framework of microbial pathogenesis, infectious diseases are one outcome of a host-microorganism interaction in a susceptible host. In cryptococcal disease, damage to the host is caused by Cryptococcus neoformans virulence determinants, the nature of the host response, or both. Further, the disease may be acute or reactivated from a latent state. Hence, a vaccine for C. neoformans would need to prevent disease resulting from either acute or reactivated infection. The evidence to support the development of a vaccine for C. neoformans that induces antibody-mediated immunity is discussed herein.     

The worm has turned--microbial virulence modeled in Caenorhabditis elegans

The nematode Caenorhabditis elegans is emerging as a facile and economical model host for the study of evolutionarily conserved mechanisms of microbial pathogenesis and innate immunity. A rapidly growing number of human and animal microbial pathogens have been shown to injure and kill nematodes. In many cases, microbial genes known to be important for full virulence in mammalian models have been shown to be similarly required for maximum pathogenicity in nematodes. C. elegans has been used in mutation-based screening systems to identify novel virulence-related microbial genes and immune-related host genes, many of which have been validated in mammalian models of disease. C. elegans-based pathogenesis systems hold the potential to simultaneously explore the molecular genetic determinants of both pathogen virulence and host defense.