RESUMO
Perfluorohexane sulfonate (PFHxS) is a member of the per- and polyfluoroalkyls (PFAS) superfamily of molecules, characterized by their fluorinated carbon chains and use in a wide range of industrial applications. PFHxS and perfluorooctane sulfonate are able to accumulate in the environment and in humans with the approximated serum elimination half-life in the range of several years. More recently, some PFAS compounds have also been suggested as potential immunosuppressants. In this study, we analyze immune cell numbers in mice following 28-d repeated oral exposure to potassium PFHxS at 12, 120, 1,200, and 12,000 ng/kg/d, with resulting serum levels ranging up to â¼1,600 ng/ml, approximating ranges found in the general population and at higher levels in PFAS workers. The immunosuppressant cyclophosphamide was analyzed as a positive control. B cells, T cells, and granulocytes from the bone marrow, liver, spleen, lymph nodes, and thymus were evaluated. We found that at these exposures, there was no effect of PFHxS on major T or B cell populations, macrophages, dendritic cells, basophils, mast cells, eosinophils, neutrophils, or circulating Ab isotypes. By contrast, mice exposed to cyclophosphamide exhibited depletion of several granulocyte and T and B cell populations in the thymus, bone marrow, and spleen, as well as reductions in IgG1, IgG2b, IgG2c, IgG3, IgE, and IgM. These data indicate that exposures of up to 12,000 ng/kg of PFHxS for 28 d do not affect immune cell numbers in naive mice, which provides valuable information for assessing the risks and health influences of exposures to this compound.
Assuntos
Fluorocarbonos , Animais , Camundongos , Linfócitos B/imunologia , Linfócitos B/efeitos dos fármacos , Ácidos Sulfônicos , Linfócitos T/imunologia , Linfócitos T/efeitos dos fármacos , Feminino , Baço/imunologia , Baço/efeitos dos fármacos , Baço/citologia , Timo/efeitos dos fármacos , Timo/imunologia , Granulócitos/efeitos dos fármacos , Granulócitos/imunologia , MasculinoRESUMO
Pathology studies of SARS-CoV-2 Omicron variants of concern (VOC) are challenged by the lack of pathogenic animal models. While Omicron BA.1 and BA.2 replicate in K18-hACE2 transgenic mice, they cause minimal to negligible morbidity and mortality, and less is known about more recent Omicron VOC. Here, we show that in contrast to Omicron BA.1, BA.5-infected mice exhibited high levels of morbidity and mortality, correlating with higher early viral loads. Neither Omicron BA.1 nor BA.5 replicated in brains, unlike most prior VOC. Only Omicron BA.5-infected mice exhibited substantial weight loss, high pathology scores in lungs, and high levels of inflammatory cells and cytokines in bronchoalveolar lavage fluid, and 5- to 8-month-old mice exhibited 100% fatality. These results identify a rodent model for pathogenesis or antiviral countermeasure studies for circulating SARS-CoV-2 Omicron BA.5. Further, differences in morbidity and mortality between Omicron BA.1 and BA.5 provide a model for understanding viral determinants of pathogenicity.