Survival at older ages: are greater influenza antibody titers protective?

Antibodies are a core element of the immune system's defense against infectious diseases. We hypothesize that antibody titres might therefore be an important predictor of survival in older individuals. This is important because biomarkers that robustly measure survival have proved elusive, despite their potential utility in health care settings. We present evidence supporting the hypothesis that influenza antibody titres are associated with overall survival of older individuals, and indicate a role for biological sex in modulating this association. Since antibody titres can be modulated by vaccination, these results have important implications for public health policy on influenza control in aging populations.

Single-step genomic best linear unbiased predictor genetic parameter estimations and genome-wide associations for milk fatty acid profiles, interval from calving to first insemination, and ketosis in Holstein cattle.

Milk fatty acids (FA) have been suggested as biomarkers for early-lactation metabolic diseases and for female fertility status. The aim of the present study was to infer associations between FA, the metabolic disorder ketosis (KET), and the interval from calving to first insemination (ICF) genetically and genomically. In this regard, we focused on a single-step genomic BLUP approach, allowing consideration of genotyped and ungenotyped cows simultaneously. The phenotypic data set considered 38,375 first-lactation Holstein cows, kept in 45 large-scale co-operator herds from 2 federal states in Germany. The calving years for these cows were from 2014 to 2017. Concentrations in milk from the first official milk recording test-day for saturated, unsaturated (UFA), monounsaturated (MUFA), polyunsaturated, palmitic, and stearic (C18:0) FA were determined via Fourier-transform infrared spectroscopy. Ketosis was defined as a binary trait according to a veterinarian diagnosis key, considering diagnoses within a 6-wk interval after calving. A subset of 9,786 cows was genotyped for 40,989 SNP markers. Variance components and heritabilities for all Gaussian distributed FA and for ICF, and for binary KET were estimated by applying single-step genomic BLUP single-trait linear and threshold models, respectively. Genetic correlations were estimated in series of bivariate runs. Genomic breeding values for the single-step genomic BLUP estimations were dependent traits in single-step GWAS. Heritabilities for FA were moderate in the range from 0.09 to 0.20 (standard error = 0.02-0.03), but quite small for ICF (0.08, standard error = 0.01) and for KET (0.05 on the underlying liability scale, posterior standard deviation = 0.02). Genetic correlations between KET and UFA, MUFA, and C18:0 were large (0.74 to 0.85, posterior standard deviation = 0.14-0.19), and low positive between KET and ICF (0.17, posterior standard deviation = 0.22). Genetic correlations between UFA, MUFA, and C18:0 with ICF ranged from 0.34 to 0.46 (standard error = 0.12). In single-step GWAS, we identified a large proportion of overlapping genomic regions for the different FA, especially for UFA and MUFA, and for saturated and palmitic FA. One identical significantly associated SNP was identified for C18:0 and KET on BTA 15. However, there was no genomic segment simultaneously significantly affecting all trait categories ICF, FA, and KET. Nevertheless, some of the annotated potential candidate genes DGKA, IGFBP4, and CXCL8 play a role in lipid metabolism and fertility mechanisms, and influence production diseases in early lactation. Genetic and genomic associations indicate that Fourier-transform infrared spectroscopy FA concentrations in milk from the first official test-day are valuable predictors for KET and for ICF.

Genetic and nongenetic profiling of milk ß-hydroxybutyrate and acetone and their associations with ketosis in Holstein cows.

Ketosis is a metabolic disorder of increasing importance in high-yielding dairy cows, but accurate population-wide binary health trait recording is difficult to implement. Against this background, proper Gaussian indicator traits, which can be routinely measured in milk, are needed. Consequently, we focused on the ketone bodies acetone and ß-hydroxybutyrate (BHB), measured via Fourier-transform infrared spectroscopy (FTIR) in milk. In the present study, 62,568 Holstein cows from large-scale German co-operator herds were phenotyped for clinical ketosis (KET) according to a veterinarian diagnosis key. A sub-sample of 16,861 cows additionally had first test-day observations for FTIR acetone and BHB. Associations between FTIR acetone and BHB with KET and with test-day traits were studied phenotypically and quantitative genetically. Furthermore, we estimated SNP marker effects for acetone and BHB (application of genome-wide association studies) based on 40,828 SNP markers from 4,384 genotyped cows, and studied potential candidate genes influencing body fat mobilization. Generalized linear mixed models were applied to infer the influence of binary KET on Gaussian-distributed acetone and BHB (definition of an identity link function), and vice versa, such as the influence of acetone and BHB on KET (definition of a logit link function). Additionally, linear models were applied to study associations between BHB, acetone and test-day traits (milk yield, fat percentage, protein percentage, fat-to-protein ratio and somatic cell score) from the first test-day after calving. An increasing KET incidence was statistically significant associated with increasing FTIR acetone and BHB milk concentrations. Acetone and BHB concentrations were positively associated with fat percentage, fat-to-protein ratio and somatic cell score. Bivariate linear animal models were applied to estimate genetic (co)variance components for KET, acetone, BHB and test-day traits within parities 1 to 3, and considering all parities simultaneously in repeatability models. Pedigree-based heritabilities were quite small (i.e., in the range from 0.01 in parity 3 to 0.07 in parity 1 for acetone, and from 0.03-0.04 for BHB). Heritabilites from repeatability models were 0.05 for acetone, and 0.03 for BHB. Genetic correlations between acetone and BHB were moderate to large within parities and considering all parities simultaneously (0.69-0.98). Genetic correlations between acetone and BHB with KET from different parities ranged from 0.71 to 0.99. Genetic correlations between acetone across parities, and between BHB across parities, ranged from 0.55 to 0.66. Genetic correlations between KET, acetone, and BHB with fat-to-protein ratio and with fat percentage were large and positive, but negative with milk yield. In genome-wide association studies, we identified SNP on BTA 4, 10, 11, and 29 significantly influencing acetone, and on BTA 1 and 16 significantly influencing BHB. The identified potential candidate genes NRXN3, ACOXL, BCL2L11, HIBADH, KCNJ1, and PRG4 are involved in lipid and glucose metabolism pathways.

Phenotypic relationships, genetic parameters, genome-wide associations, and identification of potential candidate genes for ketosis and fat-to-protein ratio in German Holstein cows.

Energy demand for milk production in early lactation exceeds energy intake, especially in high-yielding Holstein cows. Energy deficiency causes increasing susceptibility to metabolic disorders. In addition to several blood parameters, the fat-to-protein ratio (FPR) is suggested as an indicator for ketosis, because a FPR >1.5 refers to high lipolysis. The aim of this study was to analyze phenotypic, quantitative genetic, and genomic associations between FPR and ketosis. In this regard, 8,912 first-lactation Holstein cows were phenotyped for ketosis according to a veterinarian diagnosis key. Ketosis was diagnosed if the cow showed an abnormal carbohydrate metabolism with increased content of ketone bodies in the blood or urine. At least one entry for ketosis in the first 6 wk after calving implied a score = 1 (diseased); otherwise, a score = 0 (healthy) was assigned. The FPR from the first test-day was defined as a Gaussian distributed trait (FPRgauss), and also as a binary response trait (FPRbin), considering a threshold of FPR = 1.5. After imputation and quality controls, 45,613 SNP markers from the 8,912 genotyped cows were used for genomic studies. Phenotypically, an increasing ketosis incidence was associated with significantly higher FPR, and vice versa. Hence, from a practical trait recording perspective, first test-day FPR is suggested as an indicator for ketosis. The ketosis heritability was slightly larger when modeling the pedigree-based relationship matrix (pedigree-based: 0.17; SNP-based: 0.11). For FPRbin, heritabilities were larger when modeling the genomic relationship matrix (pedigree-based: 0.09; SNP-based: 0.15). For FPRgauss, heritabilities were almost identical for both pedigree and genomic relationship matrices (pedigree-based: 0.14; SNP-based: 0.15). Genetic correlations between ketosis with FPRbin and FPRgauss using either pedigree- or genomic-based relationship matrices were in a moderate range from 0.39 to 0.71. Applying genome-wide association studies, we identified the specific SNP rs109896020 (BTA 5, position: 115,456,438 bp) significantly contributing to ketosis. The identified potential candidate gene PARVB in close chromosomal distance is associated with nonalcoholic fatty liver disease in humans. The most important SNP contributing to FPRbin was located within the DGAT1 gene. Different SNP significantly contributed to ketosis and FPRbin, indicating different mechanisms for both traits genomically.

Cryosurvival of in vitro produced bovine embryos supplemented with l-Carnitine and concurrent reduction of fatty acids.

Lipid accumulation is associated with reduced embryonic quality, causing limited survival after cryopreservation. Therefore, in the present study we aimed to reveal the effects of supplementation of a lipid reducing agent, l-carnitine and the removal of fatty acids during in vitro culture on the morphological as well as on the molecular level. To accomplish that, presumptive zygotes were cultured in 4 contrasting groups: namely SOFaa medium supplemented with BSA, (BSA), SOFaa medium supplemented with fatty acid free BSA (FAF), SOFaa medium supplemented with BSA as well as l-Carnitine (BSA + LC) and SOFaa medium concurrently supplemented with fatty acid free BSA and l-Carnitine (FAF + LC). Considering the developmental rates, no impact of different treatments was observed. Conversely, treatment groups clearly affected lipid content, with the lowest amounts detected in embryos derived from FAF and BSA + LC groups, implicating that both removal of fatty acids and supplementation of LC reduces lipid content effectively. Importantly, survival rates after cryopreservation show that LC significantly affects the kinetics of re-expansion, with the highest hatching rates detected for embryos cultured in FAF + LC (p < 0.05). Noteworthy, the highest cryotolerance did not go along with lowest lipid contents. Finally, metabolic alterations between the groups were reflected in different abundances of selected candidate genes related to lipid metabolism and oxidative stress response, like AMPKA1, ACC and PGC1 α or KEAP1 and SOD1. All in all, highly beneficial effects on survival rates after cryopreservation have been detected when embryos were cultured in absence of fatty acids and concurrent presence of l-Carnitine. Highest cryotolerance, however, did not correlate with lowest lipid contents.

Mathematical Modeling of Viral Zoonoses in Wildlife.

Zoonoses are a worldwide public health concern, accounting for approximately 75% of human infectious diseases. In addition, zoonoses adversely affect agricultural production and wildlife. We review some mathematical models developed for the study of viral zoonoses in wildlife and identify areas where further modeling efforts are needed.

Commensal ecology, urban landscapes, and their influence on the genetic characteristics of city-dwelling Norway rats (Rattus norvegicus).

Movement of individuals promotes colonization of new areas, gene flow among local populations, and has implications for the spread of infectious agents and the control of pest species. Wild Norway rats (Rattus norvegicus) are common in highly urbanized areas but surprisingly little is known of their population structure. We sampled individuals from 11 locations within Baltimore, Maryland, to characterize the genetic structure and extent of gene flow between areas within the city. Clustering methods and a neighbour-joining tree based on pairwise genetic distances supported an east-west division in the inner city, and a third cluster comprised of historically more recent sites. Most individuals (approximately 95%) were assigned to their area of capture, indicating strong site fidelity. Moreover, the axial dispersal distance of rats (62 m) fell within typical alley length. Several rats were assigned to areas 2-11.5 km away, indicating some, albeit infrequent, long-distance movement within the city. Although individual movement appears to be limited (30-150 m), locations up to 1.7 km are comprised of relatives. Moderate F(ST), differentiation between identified clusters, and high allelic diversity indicate that regular gene flow, either via recruitment or migration, has prevented isolation. Therefore, ecology of commensal rodents in urban areas and life-history characteristics of Norway rats likely counteract many expected effects of isolation or founder events. An understanding of levels of connectivity of rat populations inhabiting urban areas provides information about the spatial scale at which populations of rats may spread disease, invade new areas, or be eradicated from an existing area without reinvasion.

A survey of rodent-borne pathogens carried by wild-caught Norway rats: a potential threat to laboratory rodent colonies.

Unintentional infection of laboratory rodents can compromise scientific research as well as the health of the animals and animal handlers. The source of contamination often is unknown, but may be introduced by wild rats from surrounding environments. To determine whether rats in Baltimore, Maryland, USA carry infectious agents commonly found in laboratory rodent colonies, we live-trapped 162 rats during 2005 to 2006 and screened them for a panel of viruses, bacteria and parasites. Antibodies against rat coronavirus/sialodacryoadenitis virus (91.7%), Mycoplasma pulmonis (72.9%), cilia-associated respiratory bacillus (52.1%), rat parvovirus/rat minute virus (29.2%), Kilham rat virus (10.4%), Toolan's H-1 virus (10.4%), Sendai virus (4.2%) and Theiler's mouse encephalomyelitis virus (4.2%), were detected in wild-caught Norway rats. Antibodies against reovirus and pneumonia virus of mice were not detected in wild Norway rats. Endoparasites, including Nippostrongylus braziliensis (71.6%), Rodentolepis nana or Hymenolepis diminuta (34.4%), Hetarakis spumosa (24.1%) and Trichuris muris (14.8%), as well as ectoparasites (14.8%), were identified in wild-caught rats. The risk of pathogen transmission from wild-caught rats to laboratory colonies needs to be mitigated by minimizing exposures rather than assuming wild animals represent a minimal hazard.

Emergence and persistence of hantaviruses.

Hantaviral diseases have been recognized for hundreds of years but, until 1976, they had not been associated with an infectious agent. When Lee and colleagues isolated what is now known as Hantaan virus, the techniques they introduced allowed further investigations into the etiology of the classical hantavirus disease, hemorrhagic fever with renal syndrome (HFRS), now known to be caused by any of multiple hantaviruses. The discovery of hantavirus pulmonary syndrome (HPS) in the New World, and that it also can be caused by any of multiple hantaviruses (family Bunyaviridae, genus Hantavirus), has opened an entire field of epidemiologic, virologic, molecular, behavioral, and ecologic studies of these viruses. There appears to be a single hantavirus-single rodent host association, such that understanding the idiosyncrasies of each rodent host species and the ecologic variables that affect them are recognized as critical if we are to reduce human risk for infection. This chapter summarizes what is known about hantaviruses with regard to history of these viruses, their taxonomy, recognized geographical distribution, ecologic factors impacting their maintenance and spread of hantaviruses, effect of rodent behavior on hantavirus transmission, influence of host factors on susceptibility to and transmission of hantaviruses, and transmission of hantaviruses from rodents to humans. In addition, we summarize all these complexities and provide suggestions for future research directions.

A survey of zoonotic pathogens carried by Norway rats in Baltimore, Maryland, USA.

Norway rats (Rattus norvegicus) carry several zoonotic pathogens and because rats and humans live in close proximity in urban environments, there exists potential for transmission. To identify zoonotic agents carried by rats in Baltimore, Maryland, USA, we live-trapped 201 rats during 2005-2006 and screened them for a panel of viruses, bacteria, and parasites. Antibodies against Seoul virus (57.7%), hepatitis E virus (HEV, 73.5%), Leptospira interrogans (65.3%), Bartonella elizabethae (34.1%), and Rickettsia typhi (7.0%) were detected in Norway rats. Endoparasites, including Calodium hepatica (87.9%) and Hymenolepis sp. (34.4%), and ectoparasites (13.9%, primarily Laelaps echidninus) also were present. The risk of human exposure to these pathogens is a significant public health concern. Because these pathogens cause non-specific and often self-limiting symptoms in humans, infection in human populations is probably underdiagnosed.

Hormonal and immunological mechanisms mediating sex differences in parasite infection.

The prevalence and intensity of infections caused by protozoa, nematodes, trematodes, cestodes, and arthropods is higher in males than females. The primary thesis of this review is that immunological differences exist between the sexes that may underlie increased parasitism in males compared to females. Several field and laboratory studies link sex differences in immune function with circulating steroid hormones; thus, the roles of sex steroids, including testosterone, oestradiol, and progesterone, as well as glucocorticoids will be discussed. Not only can host hormones affect responses to infection, but parasites can both produce and alter hormone concentrations in their hosts. The extent to which changes in endocrine-immune interactions following infection are mediated by the host or the parasite will be considered. Although males are more susceptible than females to many parasites, there are parasites for which males are more resistant than females and endocrine-immune interactions may underlie this sex reversal. Finally, although immunological differences exist between the sexes, genetic and behavioural differences may explain some variability in response to infection and will be explored as alternative hypotheses for how differences between the sexes contribute to dimorphic responses to parasites.

Sex differences in immune responses and viral shedding following Seoul virus infection in Norway rats.

In the field, male rodents are more frequently infected with hantaviruses than females. This study examined whether patterns of immune responses against hantavirus differed between the sexes. Male and female Long Evans rats (Rattus norvegicus) were inoculated with Seoul virus, and antibody and cytokine responses, as well as virus shedding were assessed. Males were more likely to shed virus in saliva, to shed virus through multiple routes (saliva, urine, and feces), and to have viral RNA in the spleen than females. Anti-Seoul virus IgG responses were higher in males than females. In both sexes, splenic IFNgamma and IL-4 production increased following infection. After infection, males had higher Th1 immune responses (i.e., IgG2a, IFNgamma, and IL-2) than females; in contrast, Th2 immune responses (i.e., IgG1, IL-4, and IL-10) were similar between the sexes. These data suggest that immune responses to Seoul virus differ between the sexes.

Sex differences in Seoul virus infection are not related to adult sex steroid concentrations in Norway rats.

Field studies of hantavirus infection in rodents report that a higher percentage of infected individuals are males than females. To determine whether males were more susceptible to hantavirus infection than females, adult male and female Long Evans rats (Rattus norvegicus) were inoculated with doses of Seoul virus ranging from 10(-4) to 10(6) PFU. The 50% infective doses (ID(50)) were not significantly different for male and female rats (10(0.05) and 10(0.8) PFU, respectively). To determine whether sex differences in response to infection were related to circulating sex steroid hormones, sex steroid concentrations were manipulated and antibody responses and virus shedding were assessed following inoculation with the ID(90). Regardless of hormone treatment, males had higher anti-Seoul virus immunoglobulin G (IgG) and IgG2a (i.e., Th1) responses than females and IgG1 (i.e., Th2) responses similar to those of females. Males also shed virus in saliva and feces longer than females. Manipulation of sex steroids in adulthood did not alter immune responses or virus shedding, suggesting that sex steroids may organize adult responses to hantavirus earlier during ontogeny.

The effects of hormones on sex differences in infection: from genes to behavior.

Males of many species are more susceptible than females to infections caused by parasites, fungi, bacteria, and viruses. One proximate cause of sex differences in infection is differences in endocrine-immune interactions. Specifically, males may be more susceptible to infection than females because sex steroids, specifically androgens in males and estrogens in females, modulate several aspects of host immunity. It is, however, becoming increasingly more apparent that in addition to affecting host immunity, sex steroid hormones alter genes and behaviors that influence susceptibility and resistance to infection. Thus, males may be more susceptible to infection than females not only because androgens reduce immunocompetence, but because sex steroid hormones affect disease resistance genes and behaviors that make males more susceptible to infection. Consideration of the cumulative effects of sex steroid hormones on susceptibility to infection may serve to clarify current discrepancies in the literature and offer alternative hypotheses to the view that sex steroid hormones only alter susceptibility to infection via changes in host immune function.

In vitro melatonin treatment enhances splenocyte proliferation in prairie voles.

The seasonal effects of photoperiod on reproduction are mediated by melatonin, and it is hypothesized that increased immune function in short days is due to the increase in the duration of nightly melatonin secretion. Melatonin can act both directly and indirectly on target tissue within the immune system. The present study sought to tease apart the direct and indirect effects of melatonin on one aspect of immune function by examining the influence of in vitro melatonin on splenocyte proliferation in female prairie voles held in long (LD 16:8) or short (LD 8:16) days. Splenocyte proliferation in response to the T-cell mitogen concanavalin A was enhanced by the addition of melatonin in vitro, as compared to cultures receiving no melatonin. Body mass increased in short-day housed prairie voles, indicating that the animals were responsive to photoperiod. However, photoperiod did not affect splenocyte proliferation in the present study. These results support the hypothesis that melatonin exerts a direct effect on splenocyte proliferation, potentially via high-affinity melatonin receptors localized on splenocytes. The findings also indicate that, irrespective of photoperiod, melatonin exerts direct effects on splenocytes to enhance immune function.

Activation of the immune-endocrine system with lipopolysaccharide reduces affiliative behaviors in voles.

In Experiment 1, individually housed male meadow voles (Microtus pennsylvanicus) and prairie voles (Microtus ochrogaster) were injected with lipopolysaccharide (LPS) and exhibited the expected decrease in testosterone and increase in corticosterone and interleukin-1beta concentrations 3 hr later, indicating activation of the endocrine and immune systems. In Experiment 2, LPS- and saline-injected males were tethered in a 3-chamber partner preference apparatus. The time females spent in each chamber with a male, as well as the amount of time spent in social contact, was monitored. Female prairie voles, but not meadow voles, spent more time in the chamber with saline- than with LPS-injected males. LPS-injected male prairie and meadow voles engaged in less social contact with female conspecifics than did saline-injected males. These data suggest that LPS modifies physiology and behavior in male voles and that females may use these changes to discriminate healthy from potentially infected males.

Role of steroid hormones in Trichinella spiralis infection among voles.

Males are generally more susceptible to parasite infection than females. This sex difference may reflect the suppressive effects of testosterone and enhancing effects of estradiol on immune function. This study characterized the role of circulating steroid hormones in sex differences after infection with the nematode Trichinella spiralis. Because testosterone suppresses immune function and because polygynous males have higher circulating testosterone concentrations than monogamous males, sex differences in parasite burden were hypothesized to be exaggerated among polygynous meadow voles compared with monogamous prairie voles. As predicted, sex differences in response to T. spiralis infection were increased among meadow voles; males had higher worm numbers than females. Male and female prairie voles had equivalent parasite burden. Overall, prairie voles had higher worm numbers than meadow voles. Contrary to our initial prediction, differences in circulating estradiol concentrations in females, testosterone concentrations in males, and corticosterone concentrations in both sexes were not related to the observed variation in T. spiralis infection. Taken together, these data suggest that not all sex differences in parasite infection are mediated by circulating steroid hormones and that adaptive-functional explanations may provide new insight into the causes of variation in parasite infection.

Influence of social factors on immune function and reproduction.

Animals are presented with continuous energy demands that vary seasonally. For example, during the winter many small mammals and birds inhibit reproduction and growth and funnel energy into thermogenesis or cellular maintenance. As energy shortages become more severe, survival may become compromised because processes such as immune function and thermogenesis are impaired. Thus, there are trade-offs between energetically expensive processes such as reproduction and immune function. In this review, the immune function and reproduction of seasonally breeding species are evaluated in relation to social interactions. It is proposed that individuals maintain the highest degree of immune function that is energetically possible within the constraints of other survival needs, as well as growth and reproduction, in habitats in which energy requirements and availability often fluctuate. It is hypothesized that extrinsic factors, such as social environment, modulate energy allocation to reproductive and immune function and that hormonal mechanisms underlie the partitioning of energy to various physiological components.

Reproductive function in female mice lacking the gene for endothelial nitric oxide synthase.

Nitric oxide (NO) acts as a neuronal messenger in both the central and peripheral nervous systems and has been implicated in reproductive physiology and behavior. Pharmacological inhibition of nitric oxide synthase (NOS) with the nonspecific NOS inhibitor, l-N(G)-nitro-Arg-methyl ester (l-NAME), induced deficits in both the number of ovarian rupture sites and the number of oocytes recovered in the oviducts of mice. Female neuronal NOS knockout (nNOS-/-) mice have normal numbers of rupture sites, but reduced numbers of oocytes recovered following systemic injections of gonadotropins, suggesting that NO produced by nNOS accounts, in part, for deficits in ovulatory efficiency observed after l-NAME administration. Additionally, endothelial NOS knockout (eNOS-/-) mice have reduced numbers of ovulated oocytes after superovulation. Because endothelial NOS has been identified in ovarian follicles, and because of the noted reduced breeding efficiency of eNOS-/- mice, the present study sought to determine the role of NO from eNOS in mediating the number of rupture sites present after ovulation. Estrous cycle length and variability were consistently reduced in eNOS-/- females. The number of rupture sites was normal in eNOS-/- mice under natural conditions and after administration of exogenous GnRH. After exogenous gonadotropin administration, eNOS-/- females displayed a significant reduction in the number of ovarian rupture sites. Female eNOS-/- mice also produced fewer pups/litter compared to WT mice. These data suggest that NO from endothelial sources might play a role in mediating rodent ovulation and may be involved in regulation of the timing of the estrous cycle.

Lipopolysaccharide facilitates partner preference behaviors in female prairie voles.

Exposure to proinflammatory cytokines (e.g., IL-1beta) or lipopolysaccharide (LPS) produces an acute activation of the immune response and results in a repertoire of behavioral patterns collectively termed sickness behaviors. Although nonspecific responses to pathogenic infection have traditionally been viewed as maladaptive effects of infection, sickness behaviors may have significant, adaptive value for the host. One set of adaptive behaviors affected by infection among mammals and birds is mate choice. In Experiment 1, female prairie voles exhibited the expected increase in blood corticosterone concentrations in response to a 0.1 cc i.p. LPS injection (50 microg), indicating activation of the endocrine system. A separate cohort of females was injected with LPS or saline and paired for 6 h with a novel, previously unpaired male. Following the cohabitation period, LPS-injected females spent significantly more time (p < 0.05) with the familiar partner when given a choice between familiar and unfamiliar males in a three-chamber apparatus designed to test partner preferences. Saline-injected females spent significantly more time with the unfamiliar male. In Experiment 2, males injected with LPS or saline spent equal amounts of time with familiar and unfamiliar females following a 6 h cohabitation with a naive female, and therefore, did not exhibit preferences. From a proximate perspective, this study provides evidence that sickness behaviors influence female, but not male, partner preference in prairie voles.