Journal of Innate Immunity

Tế bào hồng cầu tổng hợp các thành phần chính của hệ thống tương tự bổ thể của muỗi, nhưng vai trò của chúng trong việc kích hoạt các phản ứng chống Plasmodium chưa được xác định rõ. Hiệu ứng của việc kích hoạt tín hiệu <i>Toll</i> trong tế bào hồng cầu lên sự sống sót của <i>Plasmodium</i> đã được nghiên cứu bằng cách chuyển tế bào hồng cầu hoặc huyết thanh không tế bào từ muỗi cho mà tại đó chất ức chế <i>cactus</i> đã bị làm câm. Những lần chuyển này đã làm tăng cường đáng kể khả năng miễn dịch chống Plasmodium, chỉ ra rằng tế bào hồng cầu là những nhân tố hoạt động trong việc kích hoạt hệ thống tương tự bổ thể, thông qua một hoặc nhiều yếu tố hiệu quả được điều chỉnh bởi con đường <i>Toll</i>. Phân tích so sánh các quần thể tế bào hồng cầu giữa các giống muỗi nhạy cảm G3 và giống kháng L3-5 <i>Anopheles gambiae</i> không cho thấy sự khác biệt đáng kể nào trong điều kiện cơ bản hoặc khi đáp ứng với nhiễm <i>Plasmodium berghei</i>. Phản ứng của muỗi nhạy cảm với các loài <i>Plasmodium</i> khác nhau cho thấy các động học tương tự sau khi nhiễm với <i>P. berghei,</i><i>P. yoelii</i> hoặc <i>P. falciparum,</i> nhưng mức độ đáp ứng tiên tiến mạnh mẽ hơn ở các cặp muỗi-ký sinh trùng ít tương thích hơn. Các con đường tín hiệu <i>Toll, Imd,</i><i>STAT</i> hay <i>JNK</i> không cần thiết cho sự sản xuất các yếu tố biệt hoá tế bào hồng cầu (HDF) nhằm đáp ứng với nhiễm <i>P. berghei</i>, nhưng sự gián đoạn của <i>Toll, STAT</i> hoặc <i>JNK</i> làm gián đoạn sự biệt hóa tế bào hồng cầu đáp ứng với HDF. Chúng tôi kết luận rằng tế bào hồng cầu là các nhân tố chủ chốt trung gian phản ứng chống Plasmodium của <i>A. gambiae</i>.

The autophagy pathway is an essential component of host defense against viral infection, orchestrating pathogen degradation (xenophagy), innate immune signaling, and certain aspects of adaptive immunity. Single autophagy proteins or cassettes of the core autophagy machinery can also function as antiviral factors independently of the canonical autophagy pathway. Moreover, to survive and propagate within the host, viruses have evolved a variety of strategies to evade autophagic attack and manipulate the autophagy machinery for their own benefit. This review summarizes recent advances in understanding the antiviral and proviral roles of autophagy and previously unappreciated autophagy-independent functions of autophagy-related genes.

In most animals there is a need to quickly prevent the loss of blood or equivalent fluids through inflicted injuries. In invertebrates with an open circulatory system (and sometimes a hydroskeleton as well) these losses may otherwise soon be fatal. Also, there is a need to prevent microbes that have gained access to the body through the wound from disseminating throughout the open circulatory system. Therefore, many invertebrates possess a coagulation system to prevent such accidents from having too serious consequences. In this review we discuss recent developments in a few animals – mainly arthropods – where more detailed data are available. It is likely, however, that corresponding systems are present in most phyla, but this is still unchartered territory.

Neutrophils are recruited to a site of infection or injury where they help initiate the acute inflammatory response. In instances of sterile inflammation, where no microbial threats are present, this neutrophil recruitment is mediated by the release of danger signals or damage-associated molecular patterns (DAMPs) from disrupted cells and tissues. At basal state, many of these substances are sequestered and remain hidden within the cell, but are released following the rupture of the plasma membrane. In other instances, these DAMPs are undetected by the innate immune system unless chemically or proteolytically modified by tissue damage. DAMPs may be directly detected by neutrophils themselves and modulate their recruitment to sites of damage or, alternatively, they can act on other cell types which in turn facilitate the arrival of neutrophils to a site of injury. In this review, we outline the direct and indirect effects of a number of DAMPs, notably extracellular ATP, mitochondrial formylated peptides and mitochondrial DNA, all of which are released by necrotic cells. We examine the effect of these substances on the recruitment and behaviour of neutrophils to sites of sterile injury. We also highlight research which suggests that neutrophils are actively involved in triggering the resolution phase of an inflammatory response. This review brings to light a growing body of work that demonstrates that the release of DAMPs and the ensuing influx of neutrophils plays an important functional role in the inflammatory response, even when no pathogens are present.

Innate immunity is a rapidly evolving field with novel cell types and molecular pathways being discovered and paradigms changing continuously. Innate and adaptive immune responses are traditionally viewed as separate from each other, but emerging evidence suggests that they overlap and mutually interact. Recently discovered cell types, particularly innate lymphoid cells and myeloid-derived suppressor cells, are gaining increasing attention. Here, we summarize and highlight current concepts in the field, focusing on innate immune cells as well as the inflammasome and DNA sensing which appear to be critical for the activation and orchestration of innate immunity, and may provide novel therapeutic opportunities for treating autoimmune, autoinflammatory, and infectious diseases.

Natural killer (NK) cells are a key component of innate immunity involved not only in the elimination of virus-infected or tumor cells but also in the regulation of the immune response by producing cytokines and chemokines that can activate other cellular components of innate and adaptive immunity. NK cell subsets are differentially affected by aging. Whereas CD56^bright cells are decreased in healthy elderly individuals, the CD56^dim subset is expanded. The expression of CD57, a marker of highly differentiated NK cells, is increased in the elderly; this supports the notion that a remodeling process of NK cell subsets occurs in aging with a gradual decrease in more immature CD56^bright NK cells and an increase in highly differentiated CD56^dim CD57+ NK cells. This NK cell redistribution can explain many of the phenotypic and functional changes in NK cells associated with healthy aging such as decreased proliferation and the maintenance of CD16-dependent cytotoxicity.

In vertebrates, the conversion of fibrinogen into fibrin is an essential process that underlies the establishment of the supporting protein framework required for coagulation. In invertebrates, fibrinogen-domain-containing proteins play a role in the defense response generated against pathogens; however, they do not function in coagulation, suggesting that this role has been recently acquired. Molecules containing fibrinogen motifs have been identified in numerous invertebrate organisms, and most of these molecules known to date have been linked to defense. Moreover, recent genome projects of invertebrate animals have revealed surprisingly high numbers of fibrinogen-like loci in their genomes, suggesting important and perhaps diverse functions of fibrinogen-like proteins in invertebrates. The ancestral role of molecules containing fibrinogen-related domains (FReDs) with immunity is the focus of this review, with emphasis on specific FReDs called fibrinogen-related proteins (FREPs) identified from the schistosome-transmitting mollusc <i>Biomphalaria glabrata</i>. Herein, we outline the range of invertebrate organisms FREPs can be found in, and detail the roles these molecules play in defense and protection against infection.

Historically, the prevailing view in the field of invertebrate immunity was that invertebrates that do not possess acquired adaptive immunity rely on innate mechanisms with low specificity and no memory. Several recent studies have shaken this paradigm and suggested that the immune defenses of invertebrates are more complex and specific than previously thought. Mounting evidence has shown that at least some invertebrates (mainly Ecdysozoa) show high levels of specificity in their immune responses to different pathogens, and that subsequent reexposure may result in enhanced protection (recently called ‘immune priming'). Here, we investigated immune priming in the Lophotrochozoan snail species <i>Biomphalaria glabrata,</i> following infection by the trematode pathogen <i>Schistosoma mansoni</i>. We confirmed that snails were protected against a secondary homologous infection whatever the host strain. We then investigated how immune priming occurs and the level of specificity of <i>B. glabrata</i> immune priming. In this report we confirmed that immune priming exists and we identified a genotype-dependent immune priming in the fresh-water snail <i>B. glabrata</i>.

A sufficient response of neutrophil granulocytes stimulated by interleukin (IL)-8 is vital during systemic inflammation, for example, in sepsis or severe trauma. Moreover, IL-8 is clinically used as biomarker of inflammatory processes. However, the effects of IL-8 on cellular key regulators of neutrophil properties such as the intracellular pH (pH_i) in dependence of ion transport proteins and during inflammation remain to be elucidated. Therefore, we investigated in detail the fundamental changes in pH_i, cellular shape, and chemotactic activity elicited by IL-8. Using flow cytometric methods, we determined that the IL-8-induced cellular activity was largely dependent on specific ion channels and transporters, such as the sodium-proton exchanger 1 (NHE1) and non-NHE1-dependent sodium flux. Exposing neutrophils in vitro to a proinflammatory micromilieu with N-formyl-Met-Leu-Phe, LPS, or IL-8 resulted in a diminished response regarding the increase in cellular size and pH. The detailed kinetics of the reduced reactivity of the neutrophil granulocytes could be illustrated in a near-real-time flow cytometric measurement. Last, the LPS-mediated impairment of the IL-8-induced response in neutrophils was confirmed in a translational, animal-free human whole blood model. Overall, we provide novel mechanistic insights for the interaction of IL-8 with neutrophil granulocytes and report in detail about its alteration during systemic inflammation.

Respiratory syncytial virus (RSV) is an important viral pathogen of otitis media, bronchiolitis, and pneumonia. As infection of the upper airways is a precondition for the development of these diseases, understanding RSV pathogenesis and the host response induced by RSV in this niche may enable the development of novel therapeutic strategies against this virus. We have used a microarray approach and showed that expression of the gene that encodes the antiviral protein viperin was significantly upregulated in the chinchilla nasopharynx up to 1 week after RSV challenge. Overexpression of human viperin in vitro diminished the ability of RSV to infect HeLa or A549 cells. Furthermore, transduction of the chinchilla airways with a recombinant adeno-associated virus vector that encodes <i>viperin</i> resulted in reduced titers of RSV in the nasopharyngeal lavage fluid. Collectively, these data indicated that viperin plays a significant role in the innate immune defense against RSV.