The hunters of nature treasures. The Nobel prize in physiology or medicine 2015

W 2015 r. Nagrodę Nobla w dziedzinie fizjologii i medycyny przyznano za opracowanie terapii przeciw chorobom tropikalnym, malarii i filariozom. Youyou Tu z Chin, specjalistka w dziedzinie farmakologii naturalnej, została nagrodzona za wskazanie artemizyniny w roślinie Artemisia annuata, jako leku hamującego namnażanie się zarodźca malarycznego w krwi człowieka. Satoshi Omura, mikrobiolog z Japonii i William Campbell amerykański biochemik i parazytolog, pochodzący z Irlandii, zostali nagrodzeni za zidentyfikowanie i wyizolowanie awermektyny ze szczepu bakterii Stretomyces avermicilis produkującego związek o silnej aktywności przeciwnicieniowej. Zastosowanie artemizyniny i iwermektyny ocaliło życie milionów dzieci w Afryce oraz zahamowało szerzenie się filarioz, groźnych chorób przyczyniających się do utraty wzroku i deformujących ciało ludzkie. W artykule omówiono historię odkrycia i mechanizm działania leków. Wprowadzenie globalnych programów leczenia w krajach tropikalnych przyczynia się do poprawy sytuacji ekonomicznej i społecznej na obszarach, na których choroby te dzięki lekom są coraz rzadziej notowane.The Nobel Prize in Physiology or Medicine 2015 was awarded to Youyou Tu "for her discoveries concerning a novel therapy against Malaria", and William C. Campbell and Satoshi Ōmura "for their discoveries concerning a novel therapy against infections caused by roundworm parasites". Chinese pharmacologist - Tu, identified artemisinin isolated from Artemisia annuata for inhibition of malaria development in the blood of man. Omura, microbiologist from Japan and William C. Campbell, biochemist and parasitologist from USA discovered anti-nematode activity of awermectin, extracted from bacteria Streptomyces avermicilis. Administration of drugs against malaria and filariasis salvaged millions lives, and reduced transmission of pathogens responsible for the lost vision and disability in Africa, Asia and Latin America. The history of the discoveries and mechanisms of drugs action are presented. International programs for the health introduced at the global scale have improved economic and social conditions in countries where diseases due to the treatment develop less frequently

In vivo stimulation of peritoneal cells by chitosan administered in drinking water to mice

The aim of the study was to determine immunostimulant properties of chitosan administered alimentary to BALB/c mice. We observed that chitosan feeding effected in activation of cells from the peritoneal cavity. The cells produced less nitric oxide with simultaneous enhanced activity of arginase and higher expression of receptor for IL-4. What is more, chitosan caused increased number of cells expressing MHC class II. The study confirms that chitosan can stimulate immune system what potentially makes it useful candidate for adjuvant

Differential effects of low and high molecular weight chitosan administered intraperitoneally to mice infected with heligmosomoides polygyrus

Aim of the study was to compare the effect of different molecular weight chitosan on activity of peritoneal cells of mice during immunosupression caused by adult stages of Heligmosomoides polygyrus. We observed that intraperitoneal injections of chitosan induce cell infiltration, but the activity of recruited cells differed depending on the type of polysaccharide used. Low molecular weight chitosan activated cells with inflammatory characteristics, while high molecular weight polysaccharide reduced cell responsiveness to stimulation. Although IgA titers in the peritoneal fluid were elevated, chitosan treatments had no effect on the level of infection

Evaluation of inhibitory effect of redox-active antimalarial drug against Babesia microti in mice

Babesiosis is an emerging, tick-transmitted disease caused by the intraerythrocytic parasite Babesia microti. In immunocompetent individuals, B. microti infection quickly resolves after antibabesial treatment. Immunocompromised patients and those of advanced age experience chronic and relapsing babesiosis, accompanied by severe complications and often, a fatal outcome. In these individuals, B. microti infection may persist despite multiple courses of treatment with antiprotozoal drugs. The increasing incidence of human babesiosis caused by B. microti, coupled with a growing number of immunosuppressed people who do not respond to standard antibabesial therapy, emphasises the need for new therapeutics for this protozoan infection with more effective mechanisms of action. Plasmodione, namely 3-[4-(trifluoromethyl)benzyl]-menadione, acts as a redox cycler and disrupts the redox homeostasis of Plasmodium-infected erythrocytes. The present study was designed to evaluate the potential inhibitory effect of this novel antimalarial compound against intraerythrocytic stages of B. microti in mice. Our results demonstrate that plasmodione did not reduce the level of parasitemia in B. microti-infected mice, indicating that interfering with the parasite redox balance is not an effective strategy to restrict the division of this protozoan. The mechanism of parasite resistance to plasmodione may be based on the differences in the oxidative metabolisms of Babesia and Plasmodium parasites inside infected erythrocytes. The significance of our results is discussed in relation to the development of novel antibabesial drugs based on redox-active benzylmenadiones

Regulatory function of parasites in autoimmune disease – outcome from experimental model infection

It is estimated that more than half of the nowadays known species are pathogenic parasites. Among macroparasites gastrointestinal nematodes are one of most common and having significant impact on life and health. Those organisms reveal strong, specific immune response in host, involving primary mechanisms associated with regulatory and Th2 cells. Referring to immunomodulatory abilities of helminths, parasite infections started to be considered as a possible therapy for many autoimmune diseases. Clinical trials on 2nd and 3rd stage are conducted in spite that treatment has not been recognized as safe for common use. Despite that the safety of treatment with parasites is still controversial and widely discussed. Our knowledge about mechanisms used by helminth to moderate immune response is still inadequate to predict possible effect of long lasting parasite infection on individual patients

Deciphering the Dual Role of <i>Heligmosomoides polygyrus</i> Antigens in Macrophage Modulation and Breast Cancer Cell Growth

In our study, we explored how parasitic nematodes, specifically Heligmosomoides polygyrus, influence the immune response, focusing on their potential role in tumor growth. The study aimed to understand the mechanisms by which these parasites modify immune cell activation, particularly in macrophages, and how this might create an environment conducive to tumor growth. Our methods involved analyzing the effects of H. polygyrus excretory-secretory antigens on macrophage activation and their subsequent impact on breast cancer cell lines EMT6 and 4T1. We observed that these antigens significantly increased the expression of genes associated with both pro-inflammatory and anti-inflammatory molecules, such as inducible nitric oxide synthase, TNF-α, (Tumor Necrosis Factor) Il-6 (Interleukin), and arginase. Additionally, we observed changes in the expression of macrophage surface receptors like CD11b, F4/80, and TLR4 (Toll-like receptor 4). Our findings indicate that the antigens from H. polygyrus markedly alter macrophage behavior and increase the proliferation of breast cancer cells in a laboratory setting. This study contributes to a deeper understanding of the complex interactions between parasitic infections and cancer development, highlighting the need for further research in this area to develop potential new strategies for cancer treatment

Babeszjoza — nowe wyzwanie w transfuzjologii?

Babesiosis is a tick-transmitted human blood disease caused by protozoan parasite Babesiamicroti. Recently, an increasing incidence of babesiosis has been observed outside endemicareas. The source of a growing number of human infections are blood transfusions and organtransplantations in the condition of therapeutic immunosuppression. Under such circumstances,a latent babesiosis may develop into acute blood-stage disease accompanied by severe complicationsand often fatal outcome. Unfortunately, currently available antimalarial drugs arenot effective against piroplasms. This may be due to different developmental strategies used byboth parasites inside infected erythrocytes. To establish new therapies, drugs that inhibit protozoadivisions or damage nucleic acids are searched. To prevent Babesia transmission throughblood transfusion, parasite-inactivation technologies, which weaken protozoa viability andreduce its infectivity, are used to purify blood. Additionally, there is a need to identify the mechanismthat is responsible for babesiosis relapse upon immunotherapy, in which lymphocyteswith regulatory functions play a key role.  Zarażenie pierwotniakiem Babesia microti jest przyczyną babeszjozy — choroby człowiekaprzenoszonej przez kleszcze. Od niedawna choroba ta pojawia się poza obszarami endemicznymi,gdzie jedną z przyczyn jej rozprzestrzeniania się są transfuzje krwi i przeszczepy narządóww warunkach terapeutycznej immunosupresji. W takich okolicznościach utajona chorobarozwija się w ostrą, zagrażającą życiu postać. Niestety obecnie dostępne leki stosowane przeciwpierwotniakom malarii nie są skuteczne przeciw piroplazmom. Zapewne wynika to z różnychstrategii rozwoju tych pasożytów w erytrocycie. W celu ustalenia nowych terapii bada się leki,które hamują podziały pierwotniaków lub uszkadzają ich kwasy nukleinowe. Aby obniżyćryzyko przenoszenia pasożytów z rodzaju Babesia z krwią, opracowano technologie inaktywacjipasożytów, zmniejszające ich żywotność i zakaźność. Choroba z postaci ostrej przechodziw przewlekłą, podlegającą nawrotowi, dlatego też istnieje potrzeba zidentyfikowania mechanizmu,który jest odpowiedzialny za wznowienie babeszjozy po immunoterapii, w której limfocytyz funkcjami regulacyjnymi odgrywają kluczową rolę

Colitis promotes adaptation of an intestinal nematode: a Heligmosomoides polygyrus mouse model system.

The precise mechanism of the very effective therapeutic effect of gastrointestinal nematodes on some autoimmune diseases is not clearly understood and is currently being intensively investigated. Treatment with living helminths has been initiated to reverse intestinal immune-mediated diseases in humans. However, little attention has been paid to the phenotype of nematodes in the IBD-affected gut and the consequences of nematode adaptation. In the present study, exposure of Heligmosomoides polygyrus larvae to the changed cytokine milieu of the intestine during colitis reduced inflammation in an experimental model of dextran sulphate sodium (DSS)- induced colitis, but increased nematode establishment in the moderate-responder BALB/c mouse strain. We used mass spectrometry in combination with two-dimensional Western blotting to determine changes in protein expression and changes in nematode antigens recognized by IgG1 in mice with colitis. We show that nematode larvae immunogenicity is changed by colitis as soon as 6 days post-infection; IgG1 did not recognize highly conserved proteins Lev-11 (isoform 1 of tropomyosin α1 chain), actin-4 isoform or FTT-2 isoform a (14-3-3 family) protein. These results indicate that changes in the small intestine provoked by colitis directly influence the nematode proteome. The unrecognized proteins seem to be key antigenic epitopes able to induce protective immune responses. The proteome changes were associated with weak immune recognition and increased larval adaptation and worm growth, altered localization in the intestine and increased survival of males but reduced worm fecundity. In this report, the mechanisms influencing nematode survival and the consequences of changed immunogenicity that reflect the immune response at the site colonized by the parasite in mice with colitis are described. The results are relevant to the use of live parasites to ameliorate IBD