Acquired Clinical Immunity to Malaria in Nonhuman Primates Coinfected with Schistosoma and Plasmodium Parasites.

Naturally acquired immunity to malaria develops over several years and can be compromised by concomitant infections. This study explored the influence of chronic schistosomiasis on clinical outcome and immunity to repeated malaria infection. Two groups of baboons (n = 8 each), were infected with Schistosoma mansoni cercariae to establish chronic infections. One of the two groups was treated with praziquantel (PZQ) to eliminate schistosome infection. The two groups plus a new malaria control group (n = 8) were inoculated three times with Plasmodium knowlesi parasites at 1-month intervals. Clinical data and IgG, IgG1, memory T-cell, and monocyte levels were recorded. After three P. knowlesi infections, we observed (i) reduced clinical symptoms in all groups with each subsequent infection, (ii) increased IgG and IgG1 levels in the malaria control (Pk-only) group, (iii) increased IgG, IgG1, CD14+, and CD14- CD16+ levels in the Schistosoma-treated (Schisto/PZQ+Pk) group, and (iv) significantly lower IgG and IgG1 levels compared to those of the Pk-only group, reduced CD4+ CD45RO+ levels, and increased levels of CD14- CD16+ cells in the coinfected (Schisto+Pk) group. Chronic S. mansoni infection does not compromise establishment of clinical immunity after multiple malaria infections, with nonclassical monocytes seeming to play a role. Failure to develop robust antibody and memory T cells may have a long-term impact on acquired immunity to malaria infection.

Dominance rank-associated gene expression is widespread, sex-specific, and a precursor to high social status in wild male baboons.

In humans and other hierarchical species, social status is tightly linked to variation in health and fitness-related traits. Experimental manipulations of social status in female rhesus macaques suggest that this relationship is partially explained by status effects on immune gene regulation. However, social hierarchies are established and maintained in different ways across species: While some are based on kin-directed nepotism, others emerge from direct physical competition. We investigated how this variation influences the relationship between social status and immune gene regulation in wild baboons, where hierarchies in males are based on fighting ability but female hierarchies are nepotistic. We measured rank-related variation in gene expression levels in adult baboons of both sexes at baseline and in response to ex vivo stimulation with the bacterial endotoxin lipopolysaccharide (LPS). We identified >2,000 rank-associated genes in males, an order of magnitude more than in females. In males, high status predicted increased expression of genes involved in innate immunity and preferential activation of the NF-κB-mediated proinflammatory pathway, a pattern previously associated with low status in female rhesus macaques. Using Mendelian randomization, we reconcile these observations by demonstrating that high status-associated gene expression patterns are precursors, not consequences, of high social status in males, in support of the idea that physiological condition determines who attains high rank. Together, our work provides a test of the relationship between social status and immune gene regulation in wild primates. It also emphasizes the importance of social context in shaping the relationship between social status and immune function.

Distinct gene regulatory signatures of dominance rank and social bond strength in wild baboons.

The social environment is a major determinant of morbidity, mortality and Darwinian fitness in social animals. Recent studies have begun to uncover the molecular processes associated with these relationships, but the degree to which they vary across different dimensions of the social environment remains unclear. Here, we draw on a long-term field study of wild baboons to compare the signatures of affiliative and competitive aspects of the social environment in white blood cell gene regulation, under both immune-stimulated and non-stimulated conditions. We find that the effects of dominance rank on gene expression are directionally opposite in males versus females, such that high-ranking males resemble low-ranking females, and vice versa. Among females, rank and social bond strength are both reflected in the activity of cellular metabolism and proliferation genes. However, while we observe pronounced rank-related differences in baseline immune gene activity, only bond strength predicts the fold-change response to immune (lipopolysaccharide) stimulation. Together, our results indicate that the directionality and magnitude of social effects on gene regulation depend on the aspect of the social environment under study. This heterogeneity may help explain why social environmental effects on health and longevity can also vary between measures. This article is part of the theme issue 'The centennial of the pecking order: current state and future prospects for the study of dominance hierarchies'.