Leishmaniasis is a group of neglected diseases that cause significant mortality and disability. In Brazil, the most prevalent form is cutaneous leishmaniasis, which is characterized by painless lesions despite intense inflammation and ulceration. While BALB/c mouse models exhibit hypersensitivity to inflammatory stimuli, C57BL/6 mice better mimic human-like lesion progression and nociception. This study aimed to investigate the mechanisms underlying nociception in cutaneous leishmaniasis using the C57BL/6 model. Following infection with L. amazonensis, behavioral and nociceptive tests revealed unaltered mechanical nociception and motor capacity, although thermal hyperalgesia was observed during the chronic phase. Elevated IL-1β production in lesions and upregulation of TRPV1 in dorsal root ganglia (DRG) neurons were detected via ELISA and RT-qPCR. Mice deficient in IL-1β signaling components exhibited increased thermal thresholds, highlighting the role of IL-1β in thermal hyperalgesia during chronic infection. Histological analysis of chronic lesions revealed tissue deformities, indicating desensitization to mechanical and inflammatory stimuli due to nerve terminal alterations and fibroplasia resulting from regenerative processes. Conversely, thermal hyperalgesia in the chronic phase is driven by the effects of IL-1β on thermal nociceptive DRG neurons. These findings suggest that IL-1β and TRPV1 contribute to thermal hyperalgesia, whereas structural changes in lesions underlie mechanical desensitization. This model provides insight into the complex nociceptive mechanisms of cutaneous leishmaniasis.

Despite the current level of public immunity to SARS-CoV-2, the early inflammatory events associated with respiratory distress in COVID-19 patients are not fully elucidated. Syrian golden hamsters, facultative hibernators, recapitulate the phenotype of SARS-CoV-2-induced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)—induced severe acute lung injury seen in patients. In this study, we describe the predominance of the innate immune response in hamsters inoculated with four different SARS-CoV-2 variants, underscoring phenotypic differences among them. Severe inflammatory lung injury was chronologically associated with acute and significant weight loss, mainly in animals inoculated with A.2 and Delta variants. Omicron-infected animals had lower overall histopathology scores compared to other variants. We highlight the central role of endothelial injury and activation in the pathogenesis of experimental SARS-CoV-2 infection in hamsters, characterised by the presence of proliferative type I and type II pneumocytes with abundant surfactant expression, thereby maintaining hyperinflated alveolar fields. Additionally, there was evidence of intrapulmonary lymphatic vessel proliferation, which was accompanied by a lack of detectable microthrombosis in the lung parenchyma. However, white microthrombi were observed in lymphatic vessels. Our findings suggest that the physiological compensatory mechanisms that maintain respiratory homeostasis in Golden Syrian hamsters prevent severe respiratory distress and death after SARS-CoV-2 infection.

The golden hamster is a suitable model for studying cutaneous leishmaniasis (CL) due to Leishmania (Viannia) braziliensis . Immunopathological mechanismsare wellstablished inthe L. (L.) major-mouse model, in which IL-4 instructs a Th2 response towards progressive infection. In the present study, we evaluatedthe natural history of L. braziliensis infection from its first stagesup to lesion establishment, with the aim ofidentifyingimmunological parameters associated with the disease outcome and parasitismfate. To this end, hamsters infected with 10 ⁴ , 10 ⁵ ,or 10 ⁶ promastigoteswere monitored duringthe first hours (4h, 24h), early (15, 30 days) and late (50 days) post-infection (pi) phases. Cytokines, iNOS and arginasegene expression were quantified in the established lesions by RT-PCR. Compared to the 10 ⁵ or 10 ⁶ groups, 10 ⁴ animals presented lower lesions sizes, less tissue damage,and lower IgG levels. Basal gene expression in normal skin was high for TGF-β, and intermediary for TNF, IL-6, and IL-4.At 4hpi, no cytokine induction was observed in the 10 ⁴ group, while an upregulation of IL-6, IL-10, and IL-4 was observed in the 10 ⁶ group. At 15dpi, lesion appearance was accompanied byan increasedexpression of all assessed cytokines, markedly in the 10 ⁵ and 10 ⁶ groups. Upregulation of all investigated cytokines was observed in the late phase, although less expressive in the 10 ⁴ group. IFN-γ was the depending variable influencing tissue damage, while IL-6 was associatedto parasite load. The network correlating gene expression and clinical and laboratorial parameters indicated inoculum-independent associations at 15 and 30dpi.A strong positive network correlation was observed in the 10 ⁴ group, but not in the10 ⁵ or 10 ⁶ groups. In conclusion, IL-4, IL-6, IL-10, and TGF-β are linkedto L. braziliensisprogression . However, a balanced cytokine network is the key for an immune response able to reduce the ongoing infection and reduce pathological damage.