Innate Resistance to Leishmania amazonensis Infection in Rat Is Dependent on NOS2

Leishmania infection causes diverse clinical manifestations in humans. The disease outcome is complicated by the combination of many host and parasite factors. Inbred mouse strains vary in resistance to Leishmania major but are highly susceptible to Leishmania amazonensis infection. However, rats are highly resistant to L. amazonensis infection due to unknown mechanisms. We use the inducible nitric oxide synthase (Nos2) gene knockout rat model (Nos2−/− rat) to investigate the role of NOS2 against leishmania infection in rats. Our results demonstrated that diversion toward the NOS2 pathway is the key factor explaining the resistance of rats against L. amazonensis infection. Rats deficient in NOS2 are susceptible to L. amazonensis infection even though their immune response to infection is still strong. Moreover, adoptive transfer of NOS2 competent macrophages into Nos2−/− rats significantly reduced disease development and parasite load. Thus, we conclude that the distinct L-arginine metabolism, observed in rat macrophages, is the basis of the strong innate resistance to Leishmania. These data highlight that macrophages from different hosts possess distinctive properties and produce different outcomes in innate immunity to Leishmania infections.

IL-33 promotes innate lymphoid cell-dependent IFN-γ production required for innate immunity to Toxoplasma gondii

IL-33 is an alarmin required for resistance to the parasite Toxoplasma gondii, but its role in innate resistance to this organism is unclear. Infection with T. gondii promotes increased stromal cell expression of IL-33 and levels of parasite replication correlate with release of IL-33 in affected tissues. In response to infection, a subset of innate lymphoid cells (ILC) emerges composed of IL-33R+ NK cells and ILC1s. In Rag1-/- mice, where NK cells and ILC1 production of IFN-g mediates innate resistance to T. gondii, the loss of the IL-33R resulted in reduced ILC responses and increased parasite replication. Furthermore, administration of IL-33 to Rag1-/- mice resulted in a marked decrease in parasite burden, increased production of IFN-g and the recruitment and expansion of inflammatory monocytes associated with parasite control. These protective effects of exogenous IL-33 were dependent on endogenous IL-12p40 and the ability of IL-33 to enhance ILC production of IFN-g. These results highlight that IL-33 synergizes with IL-12 to promote ILC-mediated resistance to T. gondii.

Innate Resistance and Phosphite Treatment Affect Both the Pathogen’s and Host’s Transcriptomes in the Tanoak-Phytophthora ramorum Pathosystem

Phosphites have been used to control Sudden Oak Death; however, their precise mode of action is not fully understood. To study the mechanism of action of phosphites, we conducted an inoculation experiment on two open-pollinated tanoak families, previously found to be partially resistant. Stems of treatment group individuals were sprayed with phosphite, and seven days later, distal leaves were inoculated with the Sudden Oak Death pathogen Phytophthora ramorum. Leaves from treated and untreated control plants were harvested before and seven days after inoculation, and transcriptomes of both host and pathogen were analyzed. We found that tanoak families differed in the presence of innate resistance (resistance displayed by untreated tanoak) and in the response to phosphite treatment. A set of expressed genes associated with innate resistance was found to overlap with an expressed gene set for phosphite-induced resistance. This observation may indicate that phosphite treatment increases the resistance of susceptible host plants. In addition, genes of the pathogen involved in detoxification were upregulated in phosphite-treated plants compared to phosphite-untreated plants. In summary, our RNA-Seq analysis supports a two-fold mode of action of phosphites, including a direct toxic effect on P. ramorum and an indirect enhancement of resistance in the tanoak host.

With or without a Vaccine—A Review of Complementary and Alternative Approaches to Managing African Swine Fever in Resource-Constrained Smallholder Settings

The spectacular recent spread of African swine fever (ASF) in Eastern Europe and Asia has been strongly associated, as it is in the endemic areas in Africa, with free-ranging pig populations and low-biosecurity backyard pig farming. Managing the disease in wild boar populations and in circumstances where the disease in domestic pigs is largely driven by poverty is particularly challenging and may remain so even in the presence of effective vaccines. The only option currently available to prevent ASF is strict biosecurity. Among small-scale pig farmers biosecurity measures are often considered unaffordable or impossible to implement. However, as outbreaks of ASF are also unaffordable, the adoption of basic biosecurity measures is imperative to achieve control and prevent losses. Biosecurity measures can be adapted to fit smallholder contexts, culture and costs. A longer-term approach that could prove valuable particularly for free-ranging pig populations would be exploitation of innate resistance to the virus, which is fully effective in wild African suids and has been observed in some domestic pig populations in areas of prolonged endemicity. We explore available options for preventing ASF in terms of feasibility, practicality and affordability among domestic pig populations that are at greatest risk of exposure to ASF.

Genetic variability in the A microsatellite at SLC11A1 gene and possible implications with innate resistance against brucellosis in Algerian native goats

Sahraoui H, Madani T, Fantazi K, Chaouch Khouane A, Ameur Ameur A, Paschino P, Vacca GM, Gaouar SBS, Dettori ML. 2020. Genetic variability in the A microsatellite at SLC11A1 gene and possible implications with innate resistance against brucellosis in Algerian native goats. Biodiversitas 21: 5630-5636. Goat rearing is among the major agricultural activities practiced in Algeria. However, brucellosis represents an important threat to the goat sector and to public health. The aim of our work was to characterize the genetic variability of the A microsatellite at the 3' untranslated region (3' UTR) of SLC11A1 gene in Algerian native goat breeds as it was associated with Brucellosis genetic resistance in goat. Genomic DNA samples of 90 goats belonging to the four Algerian native breeds; Mekatia (n = 32), Arbia (n = 30), Dwarf of Kabylia (n = 14) and Mozabit (n = 14) have been analyzed. Polymorphism of region A microsatellite was determined by capillary electrophoresis identifying 8 alleles and 20 genotypes. Genetic parameters were also estimated. Polymorphic information content was PIC = 0.60, the observed and the expected heterozygosity were Ho = 0.569 and He = 0.595, respectively, and the values of FIS, FIT and FST were 0.044, 0.064, and 0.021, respectively. The A microsatellite was highly polymorphic and alleles associated genetic resistance against brucellosis in other breeds or species have been identified. These results open a promising opportunity to implement a genetic improvement program to reduce goat brucellosis spread in Algeria.