Disrupting Immune Regulation Incurs Transient Costs in Male Reproductive Function

Virginia Belloni,Bruno Faivre,Gabriele Sorci,Eugenio Paccagnini,Jérôme Bellenger,Romain Guerreiro,Benoit Foligne

doi:10.1371/journal.pone.0084606

Abstract

BackgroundImmune protection against pathogenic organisms has been shown to incur costs. Previous studies investigating the cost of immunity have mostly focused on the metabolic requirements of immune maintenance and activation. In addition to these metabolic costs, the immune system can induce damage to the host if the immune response is mis-targeted or over-expressed. Given its non-specific nature, an over-expressed inflammatory response is often associated with substantial damage for the host. Here, we investigated the cost of an over-expressed inflammatory response in the reproductive function of male mice.Methodology/Principal FindingsWe experimentally blocked the receptors of an anti-inflammatory cytokine (IL-10) in male mice exposed to a mild inflammatory challenge, with each treatment having an appropriate control group. The experiment was conducted on two age classes, young (3 month old) and old (15 month old) mice, to assess any age-related difference in the cost of a disrupted immune regulation. We found that the concomitant exposure to an inflammatory insult and the blockade of IL-10 induced a reduction in testis mass, compared to the three other groups. The frequency of abnormal sperm morphology was also higher in the group of mice exposed to the inflammatory challenge but did not depend on the blockade of the IL-10.ConclusionsOur results provide evidence that immune regulation confers protection against the risk of inflammation-induced infertility during infection. They also suggest that disruption of the effectors involved in the regulation of the inflammatory response can have serious fitness consequences even under mild inflammatory insult and benign environmental conditions.

Highlights

Ecological immunology has emerged as a discipline in the late 90th with the fundament that anti-parasite defenses cannot confer maximal protection because of the costs associated with immunity [1,2]
They suggest that disruption of the effectors involved in the regulation of the inflammatory response can have serious fitness consequences even under mild inflammatory insult and benign environmental conditions
The mortality of old mice mostly occurred in the antiIL-10R/LPS group (5/10), one individual (1/9) died in the IgG/ phosphate buffered solution (PBS) group, whereas none of the mice died in the anti-IL-10R/ PBS (0/9) and the IgG/LPS (0/9) groups (Log-Rank, x23 = 15.01, P = 0.0018) (Figure 1)

Summary

Introduction

Ecological immunology has emerged as a discipline in the late 90th with the fundament that anti-parasite defenses cannot confer maximal protection because of the costs associated with immunity [1,2]. Even though not all studies converged towards measurable costs of immunity [10,11], an overall picture emerged consistent with the view that the expression of immune defenses is constrained by the associated costs [12,2] This early work mostly neglected the costs that are induced by a misdirected or an overreacting immune response (but see [13,14]). Autoimmunity and immunopathology have understandably attracted considerable attention from biomedical scientists, but we still largely ignore how they can shape the evolution of immune defenses and parasite exploitation strategies [16,17,18,19,20] This gap on our knowledge on the fitness consequences of immunopathology has started to be filled with studied conducted on laboratory and free-ranging animals [21,22,23,24]. We investigated the cost of an over-expressed inflammatory response in the reproductive function of male mice

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