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EVOLUTION responses relevant for pathogen fitness. House
finches naïve to M. gallisepticum at capture (n =
Incomplete host immunity favors 120 finches) were individually housed and se-
quentially exposed to pairs of M. gallisepticum
strains that either were identical (homologous)
the evolution of virulence in or had different levels of virulence (heterologous),
with clinical recovery between exposures. We
an emergent pathogen performed two identical experiments in successive
years, each using three distinct pathogen strains in
a completely randomized design (Tables 1 and 2).
4
Arietta E. Fleming-Davies, 1,2,3 * Paul D. Williams, *† André A. Dhondt, 5 Positive controls received sterile medium dur-
5
2
Andrew P. Dobson, 4,6 Wesley M. Hochachka, Ariel E. Leon, David H. Ley, 7 ing primary inoculation and thus had no path-
2
8
Erik E. Osnas, Dana M. Hawley ‡ ogen exposure before secondary inoculation with
one of the six strains. We quantified strain vir-
ulence as the degree of within-host replication
Immune memory evolved to protect hosts from reinfection, but incomplete responses that (e in Tables 1 and 2) using conjunctival pathogen
allow future reinfection may inadvertently select for more-harmful pathogens. We present
loads measured by quantitative polymerase chain
empirical and modeling evidence that incomplete immunity promotes the evolution of
reaction (qPCR) (10)across8weeksafter primary
higher virulence in a natural host-pathogen system. We performed sequential infections
inoculation of immunologically naïve birds (see
of house finches with Mycoplasma gallisepticum strains of various levels of virulence.
supplementary materials). To examine how the
Virulent bacterial strains generated stronger host protection against reinfection than less
virulence of the primary and secondary strains
virulent strains and thus excluded less virulent strains from infecting previously exposed
affected host responses relevant for pathogen
hosts. In a two-strain model, the resulting fitness advantage selected for an almost twofold
fitness, we measured conjunctivitis severity and
increase in pathogen virulence. Thus, the same immune systems that protect hosts from pathogen load for 5 weeks after secondary inoc-
infection can concomitantly drive the evolution of more-harmful pathogens in nature.
ulation. Conjunctivitis severity, which correlates Downloaded from
with disease-induced mortality risk in the wild
mperfect vaccines promote the evolution of fection (6), generating pools of recovered hosts in (6, 7), was scored on an ordinal scale from 0 to 3,
more-harmful pathogens by creating a fit- wild populations. Furthermore, recovered hosts and conjunctival pathogen load was quantified
ness advantage for virulent strains in vacci- show strong but incomplete immune protection by qPCR (10).
nated hosts, such as high rates of infectivity and thus can become reinfected with homolo- First, we found that hosts with prior experi-
I or transmission (1–5). By preventing disease- gous or heterologous pathogen strains (11–13). mental exposure to any M. gallisepticum strain
induced host death and subsequent removal of In our study, we tested whether incomplete host showed reduced severity of the clinical signs that
virulent strains from a population, imperfect vac- immunity drives the evolution of greater viru- predict mortality risk in the wild (6, 7)compared
cines also reduce the overall costs of virulence to lence in this system. with hosts with no prior exposure (Fig. 1A). Thus, http://science.sciencemag.org/
pathogens (5). We asked whether incomplete We used sequential-inoculation experiments consistent with findings from earlier work using
immune responses to natural infections can sim- to quantify how incomplete immunity generated vaccines (5), host immunity reduced the costs of
ilarly favor the evolution of more-virulent path- from experimental prior exposure alters host virulence to the pathogen by protecting hosts
ogen strains that cause greater host mortality.
The bacterial pathogen Mycoplasma gallisepticum
emerged in the 1990s in free-living house finches Table 1. Relative virulence and log 10 conjunctival pathogen loads (means ± SEM) for experiment
(Haemorhous mexicanus), causing severe con- one. All birds received primary and secondary inoculations with either sterile medium or one of three
junctivitis that indirectly reduces finch survival M. gallisepticum strains that varied in virulence (10). Strains are ordered from low to high virulence on March 1, 2018
via visual impairment and reduced ability to es- (left to right and top to bottom), and relative virulence terms describe the primary exposure strain
cape predators (6, 7). After emergence in the relative to the secondary exposure strain (e.g., “less virulent” indicates primary exposure to a less
eastern United States, M. gallisepticum spread virulent strain than the secondary strain). Numbers in column headings indicate strain virulence estimated
throughout the house finch range (8), transmitted from a separate data set for naïve hosts (see supplementary materials). Strain virulence values (e)are
by direct contact and contaminated surfaces such linear model coefficients (for a linear mixed-effects model fitting strain effects in naïve birds using data
as bird feeders (9). Soon after the pathogen be- from all experimental strains; likelihood ratio = 172.56, df = 6, 124, P < 0.001), whereas values in the table
came endemic on each coast of the United States, are raw means of pathogen load (n = 4 to 5 birds for each group). Pathogen loads tend to increase top to
the virulence of circulating M. gallisepticum bottom (with increasing virulence of the secondary strain) but decrease left to right within a row (with
strains rapidly increased, as measured by dis- increasing virulence of the primary strain). N/A, not applicable.
ease severity produced in immunologically naïve
hosts (10). More than half of free-living house
finches can recover from M. gallisepticum in- Relative virulence and mean pathogen load for primary exposure
CA2006 VA1994 NC2006
Secondary Sterile medium low intermediate high
exposure (control)
1 Department of Biology, University of San Diego, San Diego, CA (e = 1.41 ± 0.34) (e = 3.31 ± 0.34) (e = 4.72 ± 0.34)
2
92110, USA. Department of Biological Sciences, Virginia
3
Tech, Blacksburg, VA 24061, USA. Department of Biology, CA2006 No prior exposure Homologous More virulent More virulent
4
0.47 ± 0.17
1.54 ± 0.23
0.20 ± 0.13
0.27 ± 0.14
Radford University, Radford, VA 24141, USA. Department of ..........................................................................................................................................................................................................................
Ecology and Evolutionary Biology, Princeton University, VA1994 No prior exposure Less virulent Homologous More virulent
5
Princeton, NJ 08544, USA. Lab of Ornithology, Cornell 3.29 ± 0.35 1.11 ± 0.31 0.62 ± 0.20 1.10 ± 0.18
6
University, Ithaca, NY 14850, USA. Santa Fe Institute, Santa ..........................................................................................................................................................................................................................
7
Fe, NM 87501, USA. Department of Population Health and NC2006 No prior exposure Less virulent Less virulent Homologous
Pathobiology, College of Veterinary Medicine, North Carolina 4.71 ± 0.52 3.30 ± 0.39 1.78 ± 0.18 1.02 ± 0.17
8
State University, Raleigh, NC 27607, USA. U.S. Fish and ..........................................................................................................................................................................................................................
Sterile medium
N/A
N/A
N/A
Negative control
Wildlife Service, Anchorage, AK 99503, USA.
0.044 ± 0.027
(control)
*These authors contributed equally to this work. †Deceased. ..........................................................................................................................................................................................................................
‡Corresponding author. Email: hawleyd@vt.edu
Fleming-Davies et al., Science 359, 1030–1033 (2018) 2 March 2018 1of4