scholarly journals Implementation of Adenovirus-Mediated Pulmonary Expression of Human ACE2 in HLA Transgenic Mice Enables Establishment of a COVID-19 Murine Model for Assessment of Immune Responses to SARS-CoV-2 Infection

Pathogens ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 940
Author(s):  
Theodor Chitlaru ◽  
Erez Bar-Haim ◽  
Liat Bar-On ◽  
Shahar Rotem ◽  
Hila Cohen ◽  
...  

HLA transgenic mice are instrumental for evaluation of human-specific immune responses to viral infection. Mice do not develop COVID-19 upon infection with SARS-CoV-2 due to the strict tropism of the virus to the human ACE2 receptor. The aim of the current study was the implementation of an adenovirus-mediated infection protocol for human ACE2 expression in HLA transgenic mice. Transient pulmonary expression of the human ACE2 receptor in these mice results in their sensitisation to SARS-CoV-2 infection, consequently providing a valuable animal model for COVID-19. Infection results in a transient loss in body weight starting 3 days post-infection, reaching 20–30% loss of weight at day 7 and full recovery at days 11–13 post-infection. The evolution of the disease revealed high reproducibility and very low variability among individual mice. The method was implemented in two different strains of HLA immunized mice. Infected animals developed strong protective humoral and cellular immune responses specific to the viral spike-protein, strictly depending on the adenovirus-mediated human ACE2 expression. Convalescent animals were protected against a subsequent re-infection with SARS-CoV-2, demonstrating that the model may be applied for assessment of efficacy of anti-viral immune responses.

Vaccine ◽  
2003 ◽  
Vol 21 (21-22) ◽  
pp. 2767-2781 ◽  
Author(s):  
Roshni Sundaram ◽  
Yiping Sun ◽  
Christopher M. Walker ◽  
Francois A. Lemonnier ◽  
Steven Jacobson ◽  
...  

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Youngwoo Cho ◽  
Saeyoull Cho

AbstractIn this study, more than 1,000 cricket (Gryllus bimaculatus) hemocytes were classified based on their size and morphology. These hemocytes were classified into six types: granulocytes, plasmatocytes, prohemocytes, spherulocytes, coagulocytes, and oenocytoids. Hemocyte cultures was observed in real time to determine which hemocytes were associated with cellular immune responses against potential pathogens. Granulocytes were identified as the professional immune cell that mediates nodulation, encapsulation, and phagocytosis of pathogens. Granulocytes have been shown to actively produce various sticky nets (amoeba-like hairs and extracellular traps) from their plasma membranes that they use to gather other hemocytes and to implement cellular immune responses. The activation of lysosomes in granulocytes started at 4 h, peaked at 12 h, and returned to baseline by 24 h post-infection. At 48 h post-infection, cells could be found within the cytoplasm of granulocytes and reactivated lysosomes surrounding these cells were visible. This result seems to reflect a phenomenon in which necrotic granulocytes are removed by other healthy granulocytes. This unique mechanism of cellular immunity is therefore a way to efficiently and effectively remove pathogens and simultaneously maintain healthy hemocytes.


2006 ◽  
Vol 13 (12) ◽  
pp. 1322-1327 ◽  
Author(s):  
Mark A. Hoffman ◽  
Christian Menge ◽  
Thomas A. Casey ◽  
William Laegreid ◽  
Brad T. Bosworth ◽  
...  

ABSTRACT Although cattle develop humoral immune responses to Shiga-toxigenic (Stx+) Escherichia coli O157:H7, infections often result in long-term shedding of these human pathogenic bacteria. The objective of this study was to compare humoral and cellular immune responses to Stx+ and Stx− E. coli O157:H7. Three groups of calves were inoculated intrarumenally, twice in a 3-week interval, with different strains of E. coli: a Stx2-producing E. coli O157:H7 strain (Stx2+O157), a Shiga toxin-negative E. coli O157:H7 strain (Stx−O157), or a nonpathogenic E. coli strain (control). Fecal shedding of Stx2+O157 was significantly higher than that of Stx−O157 or the control. Three weeks after the second inoculation, all calves were challenged with Stx2+O157. Following the challenge, levels of fecal shedding of Stx2+O157 were similar in all three groups. Both groups inoculated with an O157 strain developed antibodies to O157 LPS. Calves initially inoculated with Stx−O157, but not those inoculated with Stx2+O157, developed statistically significant lymphoproliferative responses to heat-killed Stx2+O157. These results provide evidence that infections with STEC can suppress the development of specific cellular immune responses in cattle, a finding that will need to be addressed in designing vaccines against E. coli O157:H7 infections in cattle.


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