The host response against
infection with Plasmodium commonly raises self-reactivity as a side effect, and antibody deposition in kidney has been cited as a possible cause of kidney injury during severe
malaria. In contrast, animal models show that
infection with the parasite confers long-term protection from lethal
lupus nephritis initiated by
autoantibody deposition in kidney. We have limited knowledge of the factors that make
parasite infection more likely to induce kidney damage in humans, or the mechanisms underlying protection from autoimmune
nephritis in animal models. Our experiments with the autoimmune-prone FcγR2B[KO] mice have shown that a prior
infection with P. yoelii 17XNL protects from end-stage
nephritis for a year, even when overall autoreactivity and systemic
inflammation are maintained at high levels. In this report we evaluate post-
infection alterations, such as
hemozoin accumulation and compensatory changes in immune cells, and their potential role in the kidney-specific protective effect by Plasmodium. We ruled out the role of pigment accumulation with the use of a
hemozoin-restricted P. berghei ANKA parasite, which induced a self-resolved
infection that protected from autoimmune
nephritis with the same mechanism as
parasitic infections that accumulated normal levels of
hemozoin. In contrast, adoptive transfer experiments revealed that bone marrow cells were altered by the
infection and could transmit the kidney protective effect to a new host. While changes in the frequency of bone marrow cell populations after
infection were variable and unique to a particular parasite strain, we detected a sustained bias in
cytokine/
chemokine expression that suggested lower fibrotic potential and higher Th1 bias likely affecting multiple cell populations. Sustained changes in bone marrow cell activation profile could have repercussions in immune responses long after the
infection was cleared.