Testosteron increases susceptibility to amebic liver abscess in mice and mediates inhibition of IFNγ secretion in natural killer T cells.

Amebic liver abscess (ALA), a parasitic disease due to infection with the protozoan Entamoeba histolytica, occurs age and gender dependent with strong preferences for adult males. Using a mouse model for ALA with a similar male bias for the disease, we have investigated the role of female and male sexual hormones and provide evidence for a strong contribution of testosterone. Removal of testosterone by orchiectomy significantly reduced sizes of abscesses in male mice, while substitution of testosterone increased development of ALA in female mice. Activation of natural killer T (NKT) cells, which are known to be important for the control of ALA, is influenced by testosterone. Specifically activated NKT cells isolated from female mice produce more IFNγ compared to NKT cells derived from male mice. This high level production of IFNγ in female derived NKT cells was inhibited by testosterone substitution, while the IFNγ production in male derived NKT cells was increased by orchiectomy. Gender dependent differences were not a result of differences in the total number of NKT cells, but a result of a higher activation potential for the CD4− NKT cell subpopulation in female mice. Taken together, we conclude that the hormone status of the host, in particular the testosterone level, determines susceptibility to ALA at least in a mouse model of the disease

Emergent Properties of Nanosensor Arrays: Applications for Monitoring IgG Affinity Distributions, Weakly Affined Hypermannosylation, and Colony Selection for Biomanufacturing

It is widely recognized that an array of addressable sensors can be multiplexed for the label-free detection of a library of analytes. However, such arrays have useful properties that emerge from the ensemble, even when monofunctionalized. As examples, we show that an array of nanosensors can estimate the mean and variance of the observed dissociation constant (<i>K</i>_D), using three different examples of binding IgG with Protein A as the recognition site, including polyclonal human IgG (<i>K</i>_D μ = 19 μM, σ² = 1000 mM²), murine IgG (<i>K</i>_D μ = 4.3 nM, σ² = 3 μM²), and human IgG from CHO cells (<i>K</i>_D μ = 2.5 nM, σ² = 0.01 μM²). Second, we show that an array of nanosensors can uniquely monitor weakly affined analyte interactions <i>via</i> the increased number of observed interactions. One application involves monitoring the metabolically induced hypermannosylation of human IgG from CHO using PSA-lectin conjugated sensor arrays where temporal glycosylation patterns are measured and compared. Finally, the array of sensors can also spatially map the local production of an analyte from cellular biosynthesis. As an example, we rank productivity of IgG-producing HEK colonies cultured directly on the array of nanosensors itself

Effects of sex and maternal immunity on protozoan and helminth infections

Protozoan and helminth parasites infect billions of people throughout the world and are responsible for significant morbidity and mortality of millions of people annually. Gender and cultural differences account for some dichotomy in the prevalence and intensity of infection between male and female humans. However, intrinsic differences in the biology, including the endocrine and immune systems, of male and female humans exert profound influence on disease pathogenesis. Generally, females are more resistant than males to many parasitic diseases, although exceptions exist, such as some cestode infections and Toxoplasma gondii. However, during pregnancy when a number of hormones are significantly increased and the immune system altered, females tend to be more susceptible than nonpregnant females and males to a number of parasitic infections. This is most notable for infections that rely on a helper T cell type 1 (Th1) response for resolution that is antagonized by the Th2/regulatory T (Treg) environment induced during pregnancy. As a corollary, infections that induce a strong Th1 response can disrupt pregnancy through ablating pregnancy-induced immune alterations. Some evidence is emerging that children born to mothers with parasitic infections can have lesions in their immune systems leading to tolerance or allergy as well as potential psycho-neurological changes leading to disease. There is increasing evidence that pharmacokinetics of drugs including anti-infectives can vary between the sexes. Many drugs used to treat parasitic infection (particularly protozoan infections) are far from ideal and have associated side effects. Tailored optimization of dosing regimens for men, women, and pregnant women for these drugs might be especially beneficial. New interventions optimized for sex and endocrine conditions could have greatest impact on the most disadvantaged groups in terms of susceptibility of disease including men and pregnant women