Insects Go on a STING Operation to Tackle Intracellular Invaders.

Insect immunity to extracellular microbes relies largely on the TOLL and IMD pathways. In this issue of Immunity, Goto et al. (2018) report that the IKKß-Relish module of the IMD pathway hitches up the intracellular sensor STING to activate antiviral responses in Drosophila.

Micromanaging Immunity in the Murine Host vs. the Mosquito Vector: Microbiota-Dependent Immune Responses to Intestinal Parasites.

The digestive tract plays a central role in nutrient acquisition and harbors a vast and intricate community of bacteria, fungi, viruses and parasites, collectively known as the microbiota. In recent years, there has been increasing recognition of the complex and highly contextual involvement of this microbiota in the induction and education of host innate and adaptive immune responses under homeostasis, during infection and inflammation. The gut passage and colonization by unicellular and multicellular parasite species present an immense challenge to the host immune system and to the microbial communities that provide vital support for its proper functioning. In mammals, parasitic nematodes induce distinct shifts in the intestinal microbial composition. Vice versa, the commensal microbiota has been shown to serve as a molecular adjuvant and immunomodulator during intestinal parasite infections. Moreover, similar interactions occur within insect vectors of deadly human pathogens. The gut microbiota has emerged as a crucial factor affecting vector competence in Anopheles mosquitoes, where it modulates outcomes of infections with malaria parasites. In this review, we discuss currently known involvements of the host microbiota in the instruction, support or suppression of host immune responses to gastrointestinal nematodes and protozoan parasites in mice, as well as in the malaria mosquito vector. A deeper understanding of the mechanisms underlying microbiota-dependent modulation of host and vector immunity against parasites in mammals and mosquitoes is key to a better understanding of the host-parasite relationships and the identification of more efficient approaches for intervention and treatment of parasite infections of both clinical and veterinary importance.

NF-κB-Like Signaling Pathway REL2 in Immune Defenses of the Malaria Vector Anopheles gambiae.

The blood feeding requirements of insects are often exploited by pathogens for their transmission. This is also the case of the protozoan parasites of genus Plasmodium, the causative agents of malaria. Every year malaria claims the lives of a half million people, making its vector, the Anopheles mosquito, the deadliest animal in the world. However, mosquitoes mount powerful immune responses that efficiently limit parasite proliferation. Among the immune signaling pathways identified in the main malaria vector Anopheles gambiae, the NF-κB-like signaling cascades REL2 and REL1 are essential for eliciting proper immune reactions, but only REL2 has been implicated in the responses against the human malaria parasite Plasmodium falciparum. Instead, constitutive activation of REL1 causes massive killing of rodent malaria parasites. In this review, we summarize our present knowledge on the REL2 pathway in Anopheles mosquitoes and its role in mosquito immune responses to diverse pathogens, with a focus on Plasmodium. Mosquito-parasite interactions are crucial for malaria transmission and, therefore, represent a potential target for malaria control strategies.

HIV-1 diversity, transmission dynamics and primary drug resistance in Angola.

OBJECTIVES: To assess HIV-1 diversity, transmission dynamics and prevalence of transmitted drug resistance (TDR) in Angola, five years after ART scale-up. METHODS: Population sequencing of the pol gene was performed on 139 plasma samples collected in 2009 from drug-naive HIV-1 infected individuals living in Luanda. HIV-1 subtypes were determined using phylogenetic analysis. Drug resistance mutations were identified using the Calibrated Population Resistance Tool (CPR). Transmission networks were determined using phylogenetic analysis of all Angolan sequences present in the databases. Evolutionary trends were determined by comparison with a similar survey performed in 2001. RESULTS: 47.1% of the viruses were pure subtypes (all except B), 47.1% were recombinants and 5.8% were untypable. The prevalence of subtype A decreased significantly from 2001 to 2009 (40.0% to 10.8%, P = 0.0019) while the prevalence of unique recombinant forms (URFs) increased > 2-fold (40.0% to 83.1%, P < 0.0001). The most frequent URFs comprised untypable sequences with subtypes H (U/H, n = 7, 10.8%), A (U/A, n = 6, 9.2%) and G (G/U, n = 4, 6.2%). Newly identified U/H recombinants formed a highly supported monophyletic cluster suggesting a local and common origin. TDR mutation K103N was found in one (0.7%) patient (1.6% in 2001). Out of the 364 sequences sampled for transmission network analysis, 130 (35.7%) were part of a transmission network. Forty eight transmission clusters were identified; the majority (56.3%) comprised sequences sampled in 2008-2010 in Luanda which is consistent with a locally fuelled epidemic. Very low genetic distance was found in 27 transmission pairs sampled in the same year, suggesting recent transmission events. CONCLUSIONS: Transmission of drug resistant strains was still negligible in Luanda in 2009, five years after the scale-up of ART. The dominance of small and recent transmission clusters and the emergence of new URFs are consistent with a rising HIV-1 epidemics mainly driven by heterosexual transmission.