Infection triggers tumor regression through activation of innate immunity in Drosophila

International audienceThe pioneering work of Dr. William Coley has shown that infections can stimulate the immune system and improve tumor growth control. However, the immune mechanisms responsible for the protective role of infectious agents have still not been identified. Here, we investigated the role of innate immune pathways in tumor regression by performing experimental infections in genetically modified Drosophila that develop invasive neoplastic tumors. After quantifying tumor size, through image processing, and immune gene expression with transcriptomic analyses, we analyzed the link between tumor size and pathogen-induced immune responses thanks to a combination of statistical and mathematical modeling. Drosophila larvae infected with a naturally-occurring bacterium showed a smaller tumor size compared to controls and fungus-infected larvae, thanks to an increase expression of Imd and Toll pathways. Our mathematical model reinforces this idea by showing that repeated acute infection could results in an even higher decrease in tumor size. Thus, our study suggests that infectious agents can induce tumor regression through the alteration of innate immune responses. This phenomenon, currently neglected in oncology, could have major implications for the elaboration of new preventive and immunotherapeutic strategies

Regiocontrolled syntheses of FAHFAs and LC-MS/MS differentiation of regioisomers

International audienceAn efficient regiospecific total synthesis of several branched fatty acyl hydroxyl-fatty acids (FAHFA) has been achieved from available terminal alkenes and alkynes. The key steps feature a boron trifluoride mediated epoxide ring opening with acetylide carbanions, followed by hydrogenation of the alkyne function. The carboxylic acid of the hydroxylated chains is introduced at the last step of the synthesis to allow the esterification of the branched hydroxyl group by fatty acids beforehand. The chemical syntheses of a “linear” FAHFA and a branched FAHFA analog containing a Z-olefin in the hydroxyl-fatty acid chain are also reported. A LC-MS/MS method has been developed. Several reversed phase columns were compared. Regioisomers were separated

Cancer prevalence and etiology in wild and captive animals

Despite the evolution of numerous natural cancer suppressor mechanisms (DeGregori, 2011), neoplasia has been recorded in most metazoans (Leroi et al., 2003). Although, a few exceptional species, such as the naked mole-rat (Heterocephalus glaber) and sharks have been claimed to be resistant to cancer (Finkelstein, 2005; Tian et al., 2013). Recent studies have, however, shown that even these species may develop cancer (Delaney et al., 2016; Finkelsetein, 2005) strongly suggesting that the vast majority of multicellular organisms are indeed susceptible to cancer. The frequent occurrence of cancer in metazoans suggests that neoplasia, similar to pathogens/parasites, may have a significant negative impact on host fitness in the wild (Vittecoq et al., 2013). This is supported by a recent review of wildlife cancer by McAloose and Newton (2009) demonstrating that high prevalence of cancer in, for example, Tasmanian devils (Sarcophilus harrisii) and belugas (Delphinapterus leucas) resulted in concomitant significant increase in levels of mortality and reduction in fitness. Wildlife cancer statistics are, however, highly scattered in the scientific literature and hence challenging to access. Moreover, tumors in wildlife are most commonly detected during post-mortem examination and therefore hard to confirm without histopathological examinations. However, even such analyses can be inaccurate because of high levels of autolysis (organ disintegration) (McAloose and Newton, 2009). In addition, individuals harbouring tumors often display a decrease in body condition frequently resulting in higher levels of parasite/pathogen infections and concomitant increased levels in morbidity and mortality (Vittecoq et al., 2013) further impeding a correct analysis of the ultimate cause of death. The combination of the negative effects of cancer and/or pathogen/parasite infections has also been shown to result in increased levels of predation (Vittecoq et al., 2013). In our view, the combination of the problems involved in accurately recording wildlife cancer, the increased risk of succumbing to pathogens/parasites, and/or predation has often led to a somewhat erroneous assumption that although cancer is common in domestic animals, it remains rare in the wild. If, as we suggest, cancer may be a significant determinant of animal fitness it is therefore crucial to determine cancer prevalence in the wild. The etiology and prevalence of transmissible cancers are presented and discussed in Chapter 12; this chapter will therefore focus on the prevalence and etiology of nontransmissible cancers. Via thorough searches of the available literature we provide a comprehensive and an updated list of cancer prevalence in wild animals ranging from fish to whales. We also provide a list of cancer recorded in captive animals from French Zoological parks and compare our findings to that recorded at other zoological parks. Finally we provide an updated list of cancers recorded as single cases in the wild, as well as in captive animals demonstrating that cancer occurs in nearly every taxonomic order of the animal kingdom

Cancer brings forward oviposition in the fly Drosophila melanogaster

Abstract Hosts often accelerate their reproductive effort in response to a parasitic infection, especially when their chances of future reproduction decrease with time from the onset of the infection. Because malignancies usually reduce survival, and hence potentially the fitness, it is expected that hosts with early cancer could have evolved to adjust their life-history traits to maximize their immediate reproductive effort. Despite the potential importance of these plastic responses, little attention has been devoted to explore how cancers influence animal reproduction. Here, we use an experimental setup, a colony of genetically modified flies Drosophila melanogaster which develop colorectal cancer in the anterior gut, to show the role of cancer in altering life-history traits. Specifically, we tested whether females adapt their reproductive strategy in response to harboring cancer. We found that flies with cancer reached the peak period of oviposition significantly earlier (i.e., 2 days) than healthy ones, while no difference in the length and extent of the fecundity peak was observed between the two groups of flies. Such compensatory responses to overcome the fitness-limiting effect of cancer could explain the persistence of inherited cancer-causing mutant alleles in the wild. K E Y W O R D S cancer, fecundity, life-history strategy, reproductio

Longitudinal study assessing the return of chloroquine susceptibility of Plasmodium falciparum in isolates from travellers returning from West and Central Africa, 2000–2011

International audienceChloroquine (CQ) was the main malaria therapy worldwide from the 1940s until the 1990s. Following the emergence of CQ-resistant Plasmodium falciparum, most African countries discontinued the use of CQ, and now promote artemisinin-based combination therapy as the first-line treatment. This change was generally initiated during the last decade in West and Central Africa. The aim of this study is to describe the changes in CQ susceptibility in this African region, using travellers returning from this region as a sentinel system