Increased adaptive immune responses and proper feedback regulation protect against clinical dengue

Etienne Simon-Loriere; Veasna Duong; Ahmed Tawfik; Sivlin Ung; Sowath Ly; Isabelle Casademont; Matthieu Prot; Noémie Courtejoie; Kevin Bleakley; Philippe Buchy; Arnaud Tarantola; Philippe Dussart; Tineke Cantaert; Anavaj Sakuntabhai

doi:10.1126/scitranslmed.aal5088

arXiv · 1712.05692

Increased adaptive immune responses and proper feedback regulation protect against clinical dengue

Etienne Simon-Loriere·Veasna Duong·Ahmed Tawfik·Sivlin Ung·Sowath Ly·Isabelle Casademont·Matthieu Prot·Noémie Courtejoie·Kevin Bleakley·Philippe Buchy·Arnaud Tarantola·Philippe Dussart·Tineke Cantaert·Anavaj Sakuntabhai

View original source ↗Read source document ↗Export metadata ↓

Abstract

Dengue is the most prevalent arthropod-borne viral disease. Clinical symptoms of dengue virus (DENV) infection range from classical mild dengue fever to severe, life-threatening dengue shock syndrome. However, most DENV infections cause few or no symptoms. Asymptomatic DENV-infected patients provide a unique opportunity to decipher the host immune responses leading to virus elimination without negative impact on t v 'health. We used an integrated approach of transcriptional profiling and immunological analysis comparing a Cambodian population of strictly asymptomatic viremic individuals with clinical dengue patients. Whereas inflammatory pathways and innate immune responses were similar between asymptomatic individuals and clinical dengue patients, expression of proteins related to antigen presentation and subsequent T and B cell activation pathways were differentially regulated, independent of viral load or previous DENV infection. Feedback mechanisms controlled the immune response in asymptomatic viremic individuals as demonstrated by increased activation of T cell apoptosis-related pathways and Fc$\gamma$RIIB signaling associated with decreased anti-DENV specific antibody concentrations. Taken together, our data illustrate that symptom-free DENV infection in children is determined by increased activation of the adaptive immune compartment and proper control mechanisms leading to elimination of viral infection without excessive immune activation, having implications for novel vaccine development strategies.

Explore related subjects

q-bio.PE

Keep this discovery

BibTeX RIS

Etienne Simon-Loriere, Veasna Duong, Ahmed Tawfik, Sivlin Ung, Sowath Ly, Isabelle Casademont, Matthieu Prot, Noémie Courtejoie, Kevin Bleakley, Philippe Buchy, Arnaud Tarantola, Philippe Dussart, Tineke Cantaert, Anavaj Sakuntabhai. 2017-12-11. Increased adaptive immune responses and proper feedback regulation protect against clinical dengue. https://doi.org/10.1126/scitranslmed.aal5088

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related papers

arXiv2026

Competition drives excessive recruitment in collective search

Groups that search collectively often exploit what they find by recruiting: one member directs others to a site it has found. Recruitment raises the number of members foraging at a known site, but the return per forager may fall as that number grows, so there is an intermediate optimal recruitment rate. In addition, a site may be used by more than one group. Here we analyze a model of two groups that forage from a single site whose return declines with the total number of foragers present. The two groups interact only through this shared return. The long-run outcome is either coexistence at the foraging site or monopoly by one group, and we analyze the boundary between these two outcomes. A group's best response to its rival is not monotone: it increases its own recruitment rate with the rival's recruitment rate in an attempt to preserve a monopoly, and then its recruitment rate drops discontinuously when it is no longer optimal to preserve a monopoly. We analyze how model parameters govern this shift: a group relinquishes monopoly when the site saturates at few foragers and when the rival group is small. When the two groups have comparable size there are multiple Nash equilibria, so either group may end up with the larger share. And when two equally matched groups compete, both recruit above the rate that maximizes their common return, so that each individual ends with less than it would in a single undivided group of the same total size.

q-bio.PE↗

arXiv2026

Selection Rules for Species Coexistence in a Hierarchical May-Leonard Model

One of the central challenges in evolutionary dynamics is understanding why some species combinations persist while others disappear. Although cyclic-interaction models have provided fundamental insights into biodiversity maintenance, much less is known about how hierarchical competitive interactions shape long-term community organization. Here, we investigate a hierarchical extension of the May-Leonard model, in which species interact through a directed predation chain while undergoing reproduction and mortality. Combining mean-field analysis with Monte Carlo simulations, we show that the fully coexisting state is generically unstable, causing the dynamics to evolve toward lower-dimensional coexistence states. The simulations further reveal stochastic extinctions dominating small populations with the dynamics progressively approaching the mean-field predictions as the system size increases. Rather than permitting arbitrary species combinations, the hierarchical-interaction structure dynamically constrains coexistence by selecting only specific subsets of species for long-term persistence. We show that these admissible coexistence states have a natural graph-theoretic interpretation as independent sets in the hierarchical interaction network, thereby providing general constraints on coexistence in hierarchical communities. Together, these results establish a theoretical framework linking hierarchical interactions, dynamical selection, graph topology, and biodiversity organization, extending the classical May-Leonard model beyond cyclic competition.

q-bio.PE↗

arXiv2026

Persistence of n-Species Lotka-Volterra Models with Periodic Pulses

Periodic impulsive interventions arise naturally in the management of biological populations, including chemotherapy, pesticide application, and infectious-disease treatment. We develop general conditions for permanence in n-species population models subject to periodic multiplicative pulse disturbances. Our main result provides a sufficient condition for permanence in terms of weighted long-term growth rates on a Morse decomposition of the extinction set, explicitly separating the contributions of continuous population dynamics from those of the periodic pulse. To establish this result, we transform the impulsive system into an associated autonomous continuous-time dynamical system and use this correspondence to extend classical permanence theory to periodically pulsed models. We further show that the same conditions imply robust permanence under sufficiently small perturbations to the continuous dynamics, pulse period, and pulse effects. We illustrate the framework with two Lotka-Volterra models motivated by biological control: competition between chemotherapy-sensitive and chemotherapy-resistant cancer cells, and integrated control of an agricultural pest using pesticides and parasitoids. These examples demonstrate how intervention frequency and intensity interact with underlying ecological interactions to determine whether populations coexist or are excluded. Our results provide a general framework for analyzing persistence in ecological systems subject to repeated discrete disturbances.

q-bio.PE↗