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Infection Order Outweighs the Role of CD4+ T Cells in Tertiary Flavivirus Exposure

Marzan-Rivera et al., iScience. 2022.

https://www.doi.org/10.1016/j.isci.2022.104764

The link between CD4+ T and B cells in immune responses to Dengue virus (DENV) and Zika virus (ZIKV) and their roles in cross-protection during heterologous infection are poorly known. The authors used CD4+ lymphocyte depletions to dissect the impact of cellular immunity on humoral responses during tertiary flavivirus infection in male macaques. CD4+ depletion in DENV/ZIKV–primed animals, followed by DENV, resulted in dysregulated adaptive immune responses. They show a delay in DENV-specific antibody titers and binding and neutralization in the DENV/ZIKV–primed, CD4-depleted animals but not in ZIKV/DENV–primed, CD4-depleted animals. This study confirms the role of CD4+ cells in priming an early humoral response during sequential flavivirus infections and suggests that the order of exposure affects the outcome of a tertiary infection. Supported by ORIP (P40OD012217), NIAID, and NIGMS.

Presence of Natural Killer B Cells in Simian Immunodeficiency Virus–Infected Colon That Have Properties and Functions Similar to Those of Natural Killer Cells and B Cells but Are a Distinct Cell Population

Cogswell et al., mSphere. 2022.

https://www.doi.org/10.1128/jvi.00235-22

HIV infection of the gut is associated with increased mucosal inflammation, and the role of natural killer B (NKB) cells in this process requires further investigation. In this study, the researchers used rhesus and cynomolgus macaque models to characterize the function and characteristics of NKB cells in response to simian immunodeficiency virus (SIV) infection. They reported that NKB cells can kill target cells, proliferate, and express several inflammatory cytokines. The properties of NKB cells could provide insight into the inflammation observed in the gut during SIV infection, and the individual contributions of each cytokine and receptor–ligand interaction could be explored in a future study. Supported by ORIP (P51OD011106), NIAID, and NIGMS.

Reduced Infant Rhesus Macaque Growth Rates Due to Environmental Enteric Dysfunction and Association with Histopathology in the Large Intestine

Hendrickson et al., Nature Communications. 2022.

https://www.doi.org/10.1038/s41467-021-27925-x

Researchers characterized environmental enteric (relating to the intestines) dysfunction (EED) among infant rhesus macaques (n=80, both sexes) naturally exposed to enteric pathogens commonly linked to human growth stunting. Despite atrophy and abnormalities observed in the small intestine, poor growth trajectories and low serum tryptophan (an amino acid needed for protein and enzymes) levels were correlated with increased histopathology (microscopic tissue examination for disease manifestation) in the large intestine. This study provides insight into the mechanisms underlying EED and indicates that the large intestine may be an important target for therapeutic intervention. Supported by ORIP (P51OD011092, P51OD011107) and NIGMS.