Leishmania RNA virus controls the severity of mucocutaneous leishmaniasis

Mucocutaneous leishmaniasis is caused by infections with intracellular parasites of the Leishmania Viannia subgenus, including Leishmania guyanensis. The pathology develops after parasite dissemination to nasopharyngeal tissues, where destructive metastatic lesions form with chronic inflammation. Currently, the mechanisms involved in lesion development are poorly understood. Here we show that metastasizing parasites have a high Leishmania RNA virus-1 (LRV1) burden that is recognized by the host Toll-like receptor 3 (TLR3) to induce proinflammatory cytokines and chemokines. Paradoxically, these TLR3-mediated immune responses rendered mice more susceptible to infection, and the animals developed an increased footpad swelling and parasitemia. Thus, LRV1 in the metastasizing parasites subverted the host immune response to Leishmania and promoted parasite persistence.     

In vivo imaging reveals an essential role for neutrophils in leishmaniasis transmitted by sand flies

Infection with the obligate intracellular protozoan Leishmania is thought to be initiated by direct parasitization of macrophages, but the early events following transmission to the skin by vector sand flies have been difficult to examine directly. Using dynamic intravital microscopy and flow cytometry, we observed a rapid and sustained neutrophilic infiltrate at localized sand fly bite sites. Invading neutrophils efficiently captured Leishmania major (L.m.) parasites early after sand fly transmission or needle inoculation, but phagocytosed L.m. remained viable and infected neutrophils efficiently initiated infection. Furthermore, neutrophil depletion reduced, rather than enhanced, the ability of parasites to establish productive infections. Thus, L.m. appears to have evolved to both evade and exploit the innate host response to sand fly bite in order to establish and promote disease.     

Granuloma-specific expression of Mycobacterium virulence proteins from the glycine-rich PE-PGRS family

Pathogenic mycobacteria, including the agent of tuberculosis, Mycobacterium tuberculosis, must replicate in macrophages for long-term persistence within their niche during chronic infection: organized collections of macrophages and lymphocytes called granulomas. We identified several genes preferentially expressed when Mycobacterium marinum, the cause of fish and amphibian tuberculosis, resides in host granulomas and/or macrophages. Two were homologs of M. tuberculosis PE/PE-PGRS genes, a family encoding numerous repetitive glycine-rich proteins of unknown function. Mutation of two PE-PGRS genes produced M. marinum strains incapable of replication in macrophages and with decreased persistence in granulomas. Our results establish a direct role in virulence for some PE-PGRS proteins.     

Protection against cutaneous leishmaniasis resulting from bites of uninfected sand flies

Despite the fact that Leishmania are transmitted exclusively by sand flies, none of the experimental models of leishmaniasis have established infection via sand fly bites. Here we describe a reproducible murine model of Leishmania major infection transmitted by Phlebotomus papatasi. Prior exposure of mice to bites of uninfected sand flies conferred powerful protection against Leishmania major that was associated with a strong delayed-type hypersensitivity response and with interferon-gamma production at the site of parasite delivery. These results have important implications for the epidemiology of cutaneous leishmaniasis and suggest a vaccination strategy against this and possibly other vector-borne diseases.     

A haptoglobin-hemoglobin receptor conveys innate immunity to Trypanosoma brucei in humans

The protozoan parasite Trypanosoma brucei is lysed by apolipoprotein L-I, a component of human high-density lipoprotein (HDL) particles that are also characterized by the presence of haptoglobin-related protein. We report that this process is mediated by a parasite glycoprotein receptor, which binds the haptoglobin-hemoglobin complex with high affinity for the uptake and incorporation of heme into intracellular hemoproteins. In mice, this receptor was required for optimal parasite growth and the resistance of parasites to the oxidative burst by host macrophages. In humans, the trypanosome receptor also recognized the complex between hemoglobin and haptoglobin-related protein, which explains its ability to capture trypanolytic HDLs. Thus, in humans the presence of haptoglobin-related protein has diverted the function of the trypanosome haptoglobin-hemoglobin receptor to elicit innate host immunity against the parasite.     

Salivary gland lysates from the sand fly Lutzomyia longipalpis enhance Leishmania infectivity

Leishmaniasis is a parasitic disease transmitted by phlebotomine sand flies. The role of sand fly saliva in transmission of the disease was investigated by injecting mice with Leishmania major parasites in the presence of homogenized salivary glands from Lutzomyia longipalpis. This procedure resulted in cutaneous lesions of Leishmania major that were routinely five to ten times as large and contained as much as 5000 times as many parasites as controls. With inocula consisting of low numbers of Leishmania major, parasites were detected at the site of injection only when the inoculum also contained salivary gland material. This enhancing effect of sand fly salivary glands on cutaneous leishmaniasis occurred with as little as 10 percent of the contents of one salivary gland of one fly. Material obtained from other bloodsucking arthropods could not mediate the phenomenon.     

Species interactions in a parasite community drive infection risk in a wildlife population

Most hosts, including humans, are simultaneously or sequentially infected with several parasites. A key question is whether patterns of coinfection arise because infection by one parasite species affects susceptibility to others or because of inherent differences between hosts. We used time-series data from individual hosts in natural populations to analyze patterns of infection risk for a microparasite community, detecting large positive and negative effects of other infections. Patterns remain once variations in host susceptibility and exposure are accounted for. Indeed, effects are typically of greater magnitude, and explain more variation in infection risk, than the effects associated with host and environmental factors more commonly considered in disease studies. We highlight the danger of mistaken inference when considering parasite species in isolation rather than parasite communities.     

搭配营造大芸的多种寄主林暨防风固沙林模式

根据实践经验和实地考察结果,提出以寄主与寄生物在生长期充分利用足够的阳光、风干、防风、固沙、提高植被覆盖率及适应现代节水技术为一体的相互独立、互不影响的搭配营造模式。模拟实验表明:①寄主树荫高度与地形条件、树的位置、树高度、树的弯度、时间及阳光照射角度有密切的关系;②主寄主菱形布置时每棵主寄主和寄生物都充分利用正常生长所需的阳光;③以高度不同的副寄主林从矮到高沿着主寄主与主风向按10°～45°布置,起减弱风速、分风及滞风的作用;④副寄主的阶梯型布置,起过滤作用;⑤副寄主的交错布置对过滤后的风起预防旋风和平衡作用。     

Fluorogenic substrate detection of viable intracellular and extracellular pathogenic protozoa

Viable Leishmania promastigotes and amastigotes were detected by epifluorescence microscopy with fluorescein diacetate being used to mark living parasites and the nucleic acid-binding compound ethidium bromide to stain dead cells. This procedure is superior to other assays because it is faster and detects viable intracellular as well as extracellular Leishmania. Furthermore, destruction of intracellular pathogens by macrophages is more accurately determined with fluorescein diacetate than with other stains. The procedure may have applications in programs to develop drugs and vaccines against protozoa responsible for human and animal disease.     

Comparative genomics of trypanosomatid parasitic protozoa

A comparison of gene content and genome architecture of Trypanosoma brucei, Trypanosoma cruzi, and Leishmania major, three related pathogens with different life cycles and disease pathology, revealed a conserved core proteome of about 6200 genes in large syntenic polycistronic gene clusters. Many species-specific genes, especially large surface antigen families, occur at nonsyntenic chromosome-internal and subtelomeric regions. Retroelements, structural RNAs, and gene family expansion are often associated with syntenic discontinuities that-along with gene divergence, acquisition and loss, and rearrangement within the syntenic regions-have shaped the genomes of each parasite. Contrary to recent reports, our analyses reveal no evidence that these species are descended from an ancestor that contained a photosynthetic endosymbiont.     

Infectious diseases. Has leishmaniasis become endemic in the U.S.?

Believed to be all but absent from United States, the Leishmania parasite has infected more than 1000 hunting dogs in 21 U.S. states and the Canadian province of Ontario. Nobody is claiming that the disease is about to run riot among the U.S. population. But the widespread outbreak in dogs has experts wondering whether visceral leishmaniasis--which sickens over half a million people yearly in South America, Africa, the Mediterranean, and India--has become an endemic disease in North America.     

Intracellular parasite invasion strategies

Intracellular parasites use various strategies to invade cells and to subvert cellular signaling pathways and, thus, to gain a foothold against host defenses. Efficient cell entry, ability to exploit intracellular niches, and persistence make these parasites treacherous pathogens. Most intracellular parasites gain entry via host-mediated processes, but apicomplexans use a system of adhesion-based motility called "gliding" to actively penetrate host cells. Actin polymerization-dependent motility facilitates parasite migration across cellular barriers, enables dissemination within tissues, and powers invasion of host cells. Efficient invasion has brought widespread success to this group, which includes Toxoplasma, Plasmodium, and Cryptosporidium.     

A role for the protease falcipain 1 in host cell invasion by the human malaria parasite

Cysteine proteases of Plasmodium falciparum are required for survival of the malaria parasite, yet their specific cellular functions remain unclear. We used a chemical proteomic screen with a small-molecule probe to characterize the predominant cysteine proteases throughout the parasite life cycle. Only one protease, falcipain 1, was active during the invasive merozoite stage. Falcipain 1-specific inhibitors, identified by screening of chemical libraries, blocked parasite invasion of host erythrocytes, yet had no effect on normal parasite processes such as hemoglobin degradation. These results demonstrate a specific role for falcipain 1 in host cell invasion and establish a potential new target for antimalarial therapeutics.     

二化螟绒茧蜂过寄生现象的初步研究

在室内通过对二化螟绒茧蜂过寄生现象的研究发现,二化螟绒茧蜂的蜂体大小与寄主体内寄生蜂数量呈线性负相关。而寄主育出蜂量与寄主体长呈线性正相关。一头寄主可被二化螟绒茧蜂多次产卵寄生,被产卵1～2次的寄主能正常育出绒茧蜂,且体内很少残留不能正常发育的二化螟绒茧蜂卵和幼虫,而被产卵3次以上的寄主死亡率高,即使存活,也只有部分二化螟绒茧蜂能正常钻出寄主,多数蜂幼虫和卵不能正常发育而死亡。当二化螟绒茧蜂在不同间隔时间内对寄主进行2次产卵寄生吋,均可育出正常后代,但第二次产下的蜂后代因种内竞争失败而不能正常生长发育。     

Virulence and local adaptation of a horizontally transmitted parasite

Parasites are thought to maximize the number of successfully transmitted offspring by trading off propagule production against host survival. In a horizontally transmitted microparasitic disease in Daphnia, a planktonic crustacean, increasing geographic distance between host and parasite origin was found to be correlated with a decrease in spore production and virulence. This finding indicates local adaptation of the parasite, but contradicts the hypothesis that long-standing coevolved parasites are less virulent than novel parasites. Virulence can be explained as the consequence of balancing the positive genetic correlation between host mortality and strain-specific spore production.     

Immune control of tuberculosis by IFN-gamma-inducible LRG-47

Interferon-gamma (IFN-gamma) provides an essential component of immunity to tuberculosis by activating infected host macrophages to directly inhibit the replication of Mycobacterium tuberculosis (Mtb). IFN-gamma-inducible nitric oxide synthase 2 (NOS2) is considered a principal effector mechanism, although other pathways may also exist. Here, we identify one member of a newly emerging 47-kilodalton (p47) guanosine triphosphatase family, LRG-47, that acts independently of NOS2 to protect against disease. Mice lacking LRG-47 failed to control Mtb replication, unlike those missing the related p47 guanosine triphosphatases IRG-47 or IGTP. Defective bacterial killing in IFN-gamma-activated LRG-47-/- macrophages was associated with impaired maturation of Mtb-containing phagosomes, vesicles that otherwise recruited LRG-47 in wild-type cells. Thus, LRG-47 may serve as a critical vacuolar trafficking component used to dispose of intracellular pathogens like Mtb.     

Interferon-gamma: the major mediator of resistance against Toxoplasma gondii

Mice were injected with a monoclonal antibody to interferon-gamma to examine the importance of endogenous production of this lymphokine in resistance against infection with the sporozoan parasite Toxoplasma gondii. Mice with intraperitoneal infections of T. gondii that received no antibody survived and developed chronic T. gondii infection, whereas the infected mice that received the monoclonal antibody died of toxoplasmosis. The activation of macrophages, which kill T. gondii in vivo, was inhibited by administration of the monoclonal antibody, but the production of antibodies to T. gondii was not suppressed. The fact that an antibody to interferon-gamma can eliminate resistance to acute Toxoplasma infection in mice suggests that this lymphokine is an important mediator of host resistance to this parasite.     

Tomatine and parasitic wasps: potential incompatibility of plant antibiosis with biological control

alpha-Tomatine, an alkaloid in tomato plants, is toxic to an endoparasite of a major lepidopterous pest of tomatoes. The parasite acquires the alkaloid from its host after the host ingests the alkaloid. This form of interaction creates a potential dilemma to controlling herbivorous pests through chemical antibiosis in plants.     

The role of mononuclear phagocytes in HTLV-III/LAV infection

Cells with properties characteristic of mononuclear phagocytes were evaluated for infectivity with five different isolates of the AIDS virus, HTLV-III/LAV. Mononuclear phagocytes cultured from brain and lung tissues of AIDS patients harbored the virus. In vitro-infected macrophages from the peripheral blood, bone marrow, or cord blood of healthy donors produced large quantities of virus. Virus production persisted for at least 40 days and was not dependent on host cell proliferation. Giant multinucleated cells were frequently observed in the macrophage cultures and numerous virus particles, often located within vacuole-like structures, were present in infected cells. The different virus isolates were compared for their ability to infect macrophages and T cells. Isolates from lung- and brain-derived macrophages had a significantly higher ability to infect macrophages than T cells. In contrast, the prototype HTLV-III beta showed a 10,000-fold lower ability to infect macrophages than T cells and virus production was one-tenth that in macrophage cultures infected with other isolates, indicating that a particular variant of HTLV-III/LAV may have a preferential tropism for macrophages or T cells. These results suggest that mononuclear phagocytes may serve as primary targets for infection and agents for virus dissemination and that these virus-infected cells may play a role in the pathogenesis of the disease.     

蜂密度和寄主卵密度对玉米螟赤眼蜂寄生效能的影响

在实验室内以米蛾卵作寄主研究了蜂密度和寄主密度对玉米螟赤眼蜂寄生效能的影响。在第一个试验中,1、2、4和8头1日龄的玉米螟赤眼蜂雌蜂被分别接入400粒米蛾卵上,结果表明,卵的总寄生率在最高蜂密度(8头)时显著高于其他蜂密度,但平均每头雌蜂的寄生率却随蜂密度的增加而减少,当蜂密度从1增加到8头时,平均每头雌蜂的寄生率几乎减少了近一半,同时每雌产后代数也随蜂密度的增加而减少,说明蜂密度的增加降低了玉米螟赤眼蜂的寄生效能．另一试验中,50、100、200和400粒米蛾卵上分别接入1头1日龄的赤眼蜂雌蜂,结果表明,随寄主卵密度的增加,卵的总寄生率也显著增加,寄主卵密度每增加1梯度,每雌产后代数平均增加了2倍,由此可以看出,寄主卵密度的增加对玉米螟赤眼蜂的寄生效能有增强作用。