Jakob Habib

Blood B Cell and Regulatory Subset Content in Multiple Sclerosis Patients

Objective B cell targeted therapies have been effective in slowing multiple sclerosis (MS) disease progression suggesting a direct causal link for this lymphoid subset. A small subset of B cells with regulative properties (Bregs) exists in peripheral blood, and induction of Bregs ameliorates experimental autoimmune encephalomyelitis (EAE), the murine model for MS. Therefore the frequency of B cell subsets and regulatory B cells in particular in peripheral blood of MS patients is of interest. Methods The phenotype and frequency of B cell subsets in peripheral blood from 32 MS patients and 34 healthy controls (HC) were examined using flow cytometry. Results We found that there is an increase in CD19+ cell number in MS 1347 ± 159 cells/μL, (average ± SEM) compared to HC, 935 ± 129 cells/μL and no apparent deficiency in B-cells with a regulatory phenotype. In addition, we observed a loss of correlation between CD19+ B cells and total lymphocyte count in MS. Conclusion These findings suggest altered blood B-cell homeostasis in MS patients.

Postnatal Zika virus infection is associated with persistent abnormalities in brain structure, function, and behavior in infant macaques

Zika virus infection early after birth has deleterious effects on the developing brain and long-term behavioral changes in rhesus macaques. Postnatal perturbation by Zika virus Much of the concern surrounding Zika virus infections focuses on fetuses infected in utero. Mavigner et al. reasoned that this neurotropic virus may have deleterious effects even after birth, so they set up a postnatal infection model to investigate. They found that infant rhesus macaques infected with Zika virus also had peripheral and central nervous system pathology. Longitudinal magnetic resonance imaging studies revealed that macaques that had been infected with Zika virus had structural and functional abnormalities and also altered emotional responses. These differences persisted months after the virus had been cleared. Although the work involved a small number of animals, their results suggest that infants and young children exposed to Zika virus should undergo more than just routine monitoring. The Zika virus (ZIKV) epidemic is associated with fetal brain lesions and other serious birth defects classified as congenital ZIKV syndrome. Postnatal ZIKV infection in infants and children has been reported; however, data on brain anatomy, function, and behavioral outcomes following infection are absent. We show that postnatal ZIKV infection of infant rhesus macaques (RMs) results in persistent structural and functional alterations of the central nervous system compared to age-matched controls. We demonstrate ZIKV lymphoid tropism and neurotropism in infant RMs and histopathologic abnormalities in the peripheral and central nervous systems including inflammatory infiltrates, astrogliosis, and Wallerian degeneration. Structural and resting-state functional magnetic resonance imaging (MRI/rs-fMRI) show persistent enlargement of lateral ventricles, maturational changes in specific brain regions, and altered functional connectivity (FC) between brain areas involved in emotional behavior and arousal functions, including weakened amygdala-hippocampal connectivity in two of two ZIKV-infected infant RMs several months after clearance of ZIKV RNA from peripheral blood. ZIKV infection also results in distinct alterations in the species-typical emotional reactivity to acute stress, which were predicted by the weak amygdala-hippocampal FC. We demonstrate that postnatal ZIKV infection of infants in this model affects neurodevelopment, suggesting that long-term clinical monitoring of pediatric cases is warranted.

Increased Immune Activation and Exhaustion in HIV-infected Youth

Background: Immune activation and exhaustion drive several comorbidities and disease progression in HIV-infected adults; however, they are not well studied in HIV-infected youth. Thus, this study sought to examine levels of immune activation and exhaustion in this population, investigate associated HIV- and non-HIV-related variables and compare results with a matched healthy control group. Methods: HIV-infected youth 8–25 years of age on stable antiretroviral therapy with an HIV-1 RNA level <1000 copies/mL were enrolled, along with matched healthy controls. We measured T-cell and monocyte immune activation and exhaustion markers in cryopreserved peripheral blood mononuclear cell and plasma samples. Results: A total of 136 subjects (80 HIV+: 66% male; 91% black) were enrolled. Markers of CD4+ and CD8+ T-cell activation were higher in the HIV-infected group versus controls [mean % CD4+CD38+HLA-DR+ and CD8+CD38+HLA-DR+ = 2.2 versus 1.5 (P=0.002) and 4.9 versus 2.2 (P<0.0001), respectively], as were exhausted CD4+ and CD8+ T-cells [mean % CD4+CD38+HLA-DR+PD-1+ and CD8+CD38+HLA-DR+PD-1+ = 1.0 versus 0.5 (P<0.0001) and 1.6 versus 0.7 (P<0.0001), respectively]. There were no differences in proportions of inflammatory or patrolling monocytes between groups (P>0.05); however, soluble CD14 was higher in HIV-infected compared with controls (1.6 versus 1.4 µg/mL; P=0.01). Current CD4 count, low-density lipoprotein cholesterol and age were the variables most associated with CD4+ and CD8+ T-cell activation. Conclusions: CD4+ and CD8+ T-cell immune activation and exhaustion are higher in HIV-infected youth compared with matched controls, while monocyte subpopulations are not altered despite a high soluble CD14 level. The clinical significance of the increased immune activation and exhaustion should be further explored.

Effects of Evolutionary History on Adaptation in Bean Beetles, a Model System for Inquiry-based Laboratories

BackgroundCurrent reforms in undergraduate biology education are advancing research experiences in laboratory courses. Such experiences in evolutionary biology have largely been limited to microbial systems.MethodsWe designed a guided-inquiry experiment in which students examine the effect of evolutionary history on the potential for adaptation in the bean beetle (Callosobruchus maculatus), an insect model system widely used in evolutionary biology research. Bean beetles lay their eggs on a variety of species of dried beans (seeds of species in the Fabaceae) and the larvae develop within the bean. They are an ideal model system for studies of experimental evolution in teaching laboratories as they are easy to rear, handle and manipulate. In this study, students design an experiment to determine if adaptation to a particular bean host pre-adapts their offspring to be more successful on a new bean host.ResultsPreliminary experiments by our students suggest that beetles adapted to a lower quality host (adzuki beans, Vigna angularis) are more successful on a new higher quality host (black-eyed peas, Vigna unguiculata) than beetles adapted to a higher quality host (mung beans, Vigna radiata). However, beetles adapted to black-eyed peas are more successful on mung beans than adzuki beans.ConclusionsTaken together, their results show that an evolutionary history on a low quality host might allow bean beetles to be more successful at invading new hosts.