The acute phase response (APR) is an important first-line defense against microparasites (e.g., bacteria, viruses) that is broadly conserved across vertebrates. However, the magnitude and duration of the APR, which includes fever, sickness behaviors (e.g., lethargy, anorexia), production of pro-inflammatory cytokines, and upregulation of anti-microbial peptides are highly variable across individuals, populations, and species. Laboratory studies have identified many drivers of variability in the APR, including organisms’ social surroundings, type of infectious agent, whether animals are co-infected with multiple parasites, and even the order in which animals became co-infected. However, studies of the APR that can replicate the natural contexts experienced by animals in the wild are rare. Such studies are particularly important, however, as they may offer insights not possible in lab settings. This thesis builds upon prior lab results by incorporating more natural experimental context to uncover the importance of two potential drivers of variation in the APR, one external and one internal: social context (external) and co-infection with gut helminths (internal).

To test an external driver of APR variation, I manipulated social context in flocks of house sparrows (Passer domesticus) kept in outdoor aviaries (chapter 2). Specifically, I varied the proportion of an animal’s social group that experienced a simulated infection (injection with lipopolysaccharide (LPS), a reliable inducer of the APR). Injected birds in flocks where all members were undergoing an APR expressed higher fevers than did birds in flocks where only half the group was experiencing a simulated infection. Despite these social context-associated differences in thermoregulation, I detected no differences in activity levels (sickness behaviors) between LPS-injected birds in different social contexts.

I also investigated an internal driver of APR variation, helminth co-infection (chapters 3-4). Helminth-driven immunomodulation is frequently reported in studies on lab mice, but this phenomenon has not been studied in songbirds. In chapter 3, I report negative correlations between helminth infection burden and the severity of the APR within and between populations of song sparrows (Melospiza melodia). In chapter 4, I tested these association using experimental anthelminthic drug treatments paired with simulated bacterial infection (LPS injection in the higher-latitude population of birds (which had higher helminth burdens). Birds given both anthelminthic drugs and simulated bacterial infections expressed higher temperatures during the first night after LPS-injections were administered, but their activity levels did not differ from LPS-injected birds with intact helminth infections.

Collectively, these experiments improve the existing knowledge of external and internal drivers on the APR in wild birds. Most notably, the two components of the APR investigated here (fever and lethargy) were decoupled under different social contexts and states of co-infection. Because physiological and behavioral responses to infection (e.g., fever and lethargy) could have very different impacts on disease outcomes and pathogen transmission, further exploration of the mechanisms underlying this decoupling is needed.