Cooperative Role of Macrophages and Neutrophils in Host Antiprotozoan Resistance in Mice Acutely Infected with Cryptosporidium parvum

Abstract

ABSTRACT Severe experimental infections with Cryptosporidium parvum have been reported in immunocompromised animals such as SCID mice (mice without functional T cells and B cells). In a C. parvum infection with 1 × 10 6 oocysts/mouse in SCID beige (SCIDbg) mice (SCID mice lacking functional NK cells), oocyst shedding was first demonstrated 18 days after infection. However, shedding was shown as early as 3 days after the same infection in SCIDbgMN mice. All of the SCIDbgMN mice died within 16 days of C. parvum infection, while 100% of the SCIDbg mice exposed to the parasite survived. SCIDbgMN mice are SCIDbg mice depleted of functional macrophages (Mφ) and neutrophils (PMN), suggesting that the severity early after C. parvum infection is strongly influenced by the functions of Mφ and PMN. All SCIDbgMN mice orally infected with a lethal dose of C. parvum survived after they were inoculated with Mφ from SCIDbg mice exposed to C. parvum (CP-Mφ) or resident Mφ previously cultured with PMN from C. parvum -infected SCIDbg mice (CP-PMN). However, all SCIDbgMN mice inoculated with CP-PMN alone or resident Mφ alone died after C. parvum infection. CP-Mφ were identified as classically activated Mφ (M1Mφ), and CP-PMN were characterized as PMN-I. In in vitro studies, resident Mφ converted to M1Mφ after transwell cultivation with CP-PMN. These results indicate that the resistance of SCIDbg mice early after C. parvum infection is displayed through the function of M1Mφ which are converted from resident Mφ influenced by CP-PMN (PMN-I).