抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Pathogen Recognition and Innate Immunity

The lion's share of bacteria in various environments cannot be cloned in the laboratory and thus cannot be sequenced using existing technologies. A major goal of single-cell genomics is to complement gene-centric metagenomic data with whole-genome assemblies of uncultivated organisms. Assembly of single-cell data is challenging because of highly non-uniform read coverage as well as elevated levels of sequencing errors and chimeric reads. We describe SPAdes, a new assembler for both single-cell and standard (multicell) assembly, and demonstrate that it improves on the recently released E+V-SC assembler (specialized for single-cell data) and on popular assemblers Velvet and SoapDeNovo (for multicell data). SPAdes generates single-cell assemblies, providing information about genomes of uncultivatable bacteria that vastly exceeds what may be obtained via traditional metagenomics studies. SPAdes is available online ( http://bioinf.spbau.ru/spades ). It is distributed as open source software.

SPAdes, a new genome assembly algorithm and its applications to single-cell sequencing ( 7th Annual SFAF Meeting, 2012)

Ferroptosis: An Iron-Dependent Form of Nonapoptotic Cell Death

The innate immune system in drosophila and mammals senses the invasion of microorganisms using the family of Toll receptors, stimulation of which initiates a range of host defense mechanisms. In drosophila antimicrobial responses rely on two signaling pathways: the Toll pathway and the IMD pathway. In mammals there are at least 10 members of the Toll-like receptor (TLR) family that recognize specific components conserved among microorganisms. Activation of the TLRs leads not only to the induction of inflammatory responses but also to the development of antigen-specific adaptive immunity. The TLR-induced inflammatory response is dependent on a common signaling pathway that is mediated by the adaptor molecule MyD88. However, there is evidence for additional pathways that mediate TLR ligand-specific biological responses.

Toll-like receptors.

Eukaryotic cells can initiate several distinct programmes of self-destruction, and the nature of the cell death process (non-inflammatory or proinflammatory) instructs responses of neighbouring cells, which in turn dictates important systemic physiological outcomes Pyroptosis, or caspase 1-dependent cell death, is inherently inflammatory, is triggered by various pathological stimuli, such as stroke, heart attack or cancer, and is crucial for controlling microbial infections Pathogens have evolved mechanisms to inhibit pyroptosis, enhancing their ability to persist and cause disease Ultimately, there is a competition between host and pathogen to regulate pyroptosis, and the outcome dictates life or death of the host

/pdf/pyroptosis-host-cell-death-and-inflammation-4f2vauj8tx.pdf

Pyroptosis: host cell death and inflammation

A wide variety of pathogenic microorganisms have been demonstrated to cause eukaryotic cell death, either as a consequence of infecting host cells or by producing toxic products. Pathogen-induced host cell death has been characterized as apoptosis in many of these systems. It is increasingly being

Apoptosis, pyroptosis, and necrosis: mechanistic description of dead and dying eukaryotic cells

Salmonella enterica serovar Typhimurium invades host macrophages and induces a unique caspase-1-dependent pathway of cell death termed pyroptosis, which is activated during bacterial infection in vivo. We demonstrate DNA cleavage during pyroptosis results from caspase-1-stimulated nuclease activity. Although poly(ADP-ribose) polymerase (PARP) activation by fragmented DNA depletes cellular ATP to cause lysis during oncosis, the rapid lysis characteristic of Salmonella-infected macrophages does not require PARP activity or DNA fragmentation. Membrane pores between 1.1 and 2.4 nm in diameter form during pyroptosis of host cells and cause swelling and osmotic lysis. Pore formation requires host cell actin cytoskeleton rearrangements and caspase-1 activity, as well as the bacterial type III secretion system (TTSS); however, insertion of functional TTSS translocons into the host membrane is not sufficient to directly evoke pore formation. Concurrent with pore formation, inflammatory cytokines are released from infected macrophages. This mechanism of caspase-1-mediated cell death provides additional experimental evidence supporting pyroptosis as a novel pathway of inflammatory programmed cell death.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1462-5822.2006.00751.x

Caspase-1-dependent pore formation during pyroptosis leads to osmotic lysis of infected host macrophages.

Pro-inflammatory programmed cell death.

Toll-like receptor 5 (TLR5) recognizes bacterial flagellin and activates host inflammatory responses. In this study, we examine the nature of the TLR5-flagellin interaction. With deletional, insertional and alanine-scanning mutagenesis, we precisely mapped the TLR5 recognition site on flagellin to a cluster of 13 amino acid residues that participate in intermolecular interactions within flagellar protofilaments and that are required for bacterial motility. The recognition site is buried in the flagellar filament, and monomeric flagellin, but not the filamentous molecule, stimulated TLR5. Finally, flagellin coprecipitated with TLR5, indicating close physical interaction between the molecules. These studies demonstrate the exquisite ability of the innate immune system to precisely target a conserved site on flagellin that is essential for bacterial motility.

Brad T. Cookson

Papers

Pyroptosis: host cell death and inflammation

Apoptosis, pyroptosis, and necrosis: mechanistic description of dead and dying eukaryotic cells

Caspase-1-dependent pore formation during pyroptosis leads to osmotic lysis of infected host macrophages.

Pro-inflammatory programmed cell death.

Toll-like receptor 5 recognizes a conserved site on flagellin required for protofilament formation and bacterial motility.