Sexual Dimorphisms in Innate Immunity and Responses to Infection in Drosophila melanogaster

Abstract

The sexes show profound differences in responses to infection and the development of autoimmunity. Dimorphisms in immune responses are ubiquitous across taxa, from arthropods to vertebrates. Drosophila melanogaster shows strong sex dimorphisms in immune system responses at baseline, upon pathogenic challenge, and over aging. We have performed an exhaustive survey of peer-reviewed literature on Drosophila immunity, and present a database of publications indicating the sex(es) analyzed in each study. While we found a growing interest in the community in adult immunity and in reporting both sexes, the main body of work in this field uses only one sex, or does not stratify by sex. We synthesize evidence for sexually dimorphic responses to bacterial, viral, and fungal infections. Dimorphisms may be mediated by distinct immune compartments, and we review work on sex differences in behavioral, epithelial, cellular, and systemic (fat body-mediated) immunity. Emerging work on sexually dimorphic aging of immune tissues, immune senescence, and inflammation are examined. We consider evolutionary drivers for sex differences in immune investment, highlight the features of Drosophila biology that make it particularly amenable to studies of immune dimorphisms, and discuss areas for future exploration.

Keywords: Drosophila; Drosophila melanogaster; aging; innate immunity; response to infection; sex dimorphism; sexual antagonism.

Figure 1

Composition of 2,614 articles on Drosophila immunity. (A) Categories used for all Drosophila immunity studies. Size of each rectangle is proportional to the number of articles within that category. The largest proportion are adult studies (purple; 1,366), followed by juvenile (yellow; 817), non-experimental (pink; 396), and bioinformatic (orange; 30) studies. (B) The quantity of articles published since 1990 until 21 August 2019 that use either adult (purple) or juvenile (yellow) Drosophila. (C) Quantity of adult Drosophila studies that do not report sex used (purple; 561), use females (pink; 378), use males (orange; 243), or use both sexes (yellow; 184). (D) Total number of articles that used both sexes, tagged according to experimental output. Tags are not exclusive, so some articles may have more than one tag. The tags used were gene function knock out (46), survival infection dynamics (47), fitness (39), lifespan (32), tissue specific (30), microbiome (24), signaling (19), behavioral (18), transcriptomics (16), metabolism composition (8), and proteomics (4).

Figure 2

Schematic representing sexual dimorphisms in innate immunity at basal state (A) and in physiological responses to immune challenge (B). (A) Male- and female-specific baseline conditions are depicted on the left and right of the central dashed line, respectively. Greater expression/ numbers are denoted by an upward-facing arrow, while stand-alone genes belonging to systemic or specific tissues represent sex-specific expression systemically or within that tissue, respectively. The dashed arrow represents the potential contribution made by the ovaries to observed differences in systemic transcript abundance. (B) Male (left column) and female (right column) physiological responses to viral, fungal/microsporidial, and bacterial are listed, with the causative pathogen in brackets. Increases and decreases in expression or behaviors are denoted by upward- and downward-facing arrows, respectively.