Cryptosporidiosis in Rhesus Macaques Challenged During Acute and Chronic Phases of SIV Infection

Abstract

The intestinal immune dysfunction due to loss of mucosal and peripheral CD4 + T cells in individuals with HIV/

Cryptosporidium in humans and animals—a one health approach to prophylaxis

“…The adaptive immune response to Cryptosporidium is characterized as a T‐helper 1 (Th1) response, and the importance of the adaptive immune response during Cryptosporidium infection is highlighted by the susceptibility of patients with AIDS to cryptosporidiosis, as well as the resolution of infection observed following CD4+ T lymphocyte cell reconstitution in patients given antiretroviral therapy . Low absolute CD4+ T cell counts in patients with HIV/AIDS were thought to be responsible for persistent and severe cryptosporidiosis; however, research with Simian immunodeficiency virus (SIV)‐infected macaques reported that persistent cryptosporidiosis was more dependent on SIV load and profound viral damage to gut lymphoid tissue and rapid depletion of mucosal CD4+ T cells during the acute phase of viral infection, than on declining circulating CD4+ T cell levels during chronic SIV infection . This suggests that depletion of local CD4+ T cells may be more predictive of disease severity than absolute CD4+ T cell numbers.…”

“…184,208 Low absolute CD4+ T cell counts in patients with HIV/AIDS were thought to be responsible for persistent and severe cryptosporidiosis; however, research with Simian immunodeficiency virus (SIV)-infected macaques reported that persistent cryptosporidiosis was more dependent on SIV load and profound viral damage to gut lymphoid tissue and rapid depletion of mucosal CD4+ T cells during the acute phase of viral infection, than on declining circulating CD4+ T cell levels during chronic SIV infection. 209 This suggests that depletion of local CD4+ T cells may be more predictive of disease severity than absolute CD4+ T cell numbers.…”

Systemic and Mucosal Immune Responses to Cryptosporidium—Vaccine Development

“…Though disease severity in humans is often viewed as being inversely proportional to absolute CD4+ T cell numbers, Tzipori and colleagues recently found that persistent cryptosporidiosis in macaques was more dependent on SIV load, viral damage to gut lymphoid tissue, and rapid depletion of mucosal CD4+ T cells during the acute phase of viral infection than on declining circulating CD4+ T cell levels during chronic SIV infection (79), suggesting that depletion of local CD4+ T cells may be more predictive of disease severity than absolute CD4+ T cell numbers.…”

“…Previous studies found that CD8+ T cell numbers increased during Cryptosporidium infection of macaques (79), and both CD4+ and CD8+ T cells isolated from humans with previous Cryptosporidium infection could produce IFN-γ in response to stimulation by C. hominis antigens (80). Furthermore, in vitro studies found that CD8+ T cells isolated from donors with prior exposure to Cryptosporidium were able to lyse C. parvum- infected intestinal epithelial cells in a manner dependent on the release of cytotoxic granules (81).…”

Meeting Report

“…Infection can involve the gastrointestinal, pancreatic, respiratory, and hepatobiliary systems and is often seen in immunosuppressed individuals. 39,44 The transmission is usually by the fecal-oral route. Another OI that can commonly affect the lung of immunosuppressed rhesus animals is Cercopithecine herpesvirus 3 or rhesus CMV.…”