Splenocyte apoptosis in Plasmodium berghei ANKA infection: possible role of TNF‐α and TGF‐β

Abstract

Cerebral malaria is associated with the circulating levels of tumour necrosis factor alpha (TNF-α) and transforming growth factor β (TGF-β), but association between these two cytokines and implications in splenocyte apoptosis remain largely obscured. We have evaluated the outcome of TGF-β and TNF-α production in the context of splenocyte apoptosis during Plasmodium berghei ANKA (PbA) infection. Blood-stage PbA infection confirmed blood-brain barrier disruption, disarray of white pulp, increase in percentage of sub-G0/G1 and splenocyte apoptosis. Flow cytometric analysis reveals up-regulation of Fas-L followed by caspase-8 and caspase-3 activation and signifies possible involvement of Fas-L-mediated splenocyte apoptosis. We have observed down-regulation of TGF-β and up-regulation of TNF-α in tissue and serum level, respectively, during PbA infection. Association between the production of TGF-β and the severity of malaria infection in splenocytes was verified with TGF-β inhibitor that exacerbated the apoptotic process. In contrary, TNF-α inhibitor causes significant delay in apoptotic process, but could not alter the lethality of parasite. Thus, results from this study suggest that the critical balance between TGF-β and TNF-α might have a key role on Fas-L-mediated splenocyte apoptosis during experimental cerebral malaria.

Increased Oxidative Stress and Apoptosis in Splenic Tissue of Lupus-Prone (NZB/NZW) F1 Mice Infected with Live but not Gamma Irradiated Plasmodium chabaudi

“…The histological alterations in splenic tissue sections after infection with live P. chabaudi presented as hypertrophied white pulp, has been reported previously (Achtman et al, 2003). In the current study, live P. chabaudi infection resulted in an increase in apoptotic cell death in splenic tissue sections and this is in agreement with previous studies (Keswani and Bhattacharyya, 2013). Nevertheless, the gamma irradiated P. chabaudi infected group presented, to some extent, a similar picture to that of the control group.…”

Modulation of CD11c+ lung dendritic cells in respect to TGF‐β in experimental pulmonary fibrosis

“…Different doses of SB431542 (2, 5, 10, and 20 mg/kg BW) were tested where 20 mg/kg BW was effective at decreasing TGF‐β concentration, but induced a higher mortality rate, indicating a possible toxic effect (data not shown). Therefore, we selected a maximal dose of 10 mg/kg BW in the following experiments (Keswani and Bhattacharyya, ). We standardized that at 10 mg/kg BW conc., SB431542 blocks TGF‐β expression for 48–72 h in control C57BL/6 mice after receiving single 100 μL i.p.…”

Host matrix metalloproteinases in cerebral malaria: new kids on the block against blood–brain barrier integrity?

“…On the other hand, P. berghei NK65-infected mice showed enhanced production of LT-α and several chemokines (CXCL-9/MIG, CCL-2/MCP-1, CCL-3/MIP-1α and CCL-5/RANTES), but no neurological symptoms [47,122]. A complementary study performed on the same model proposed a concurrent role for Transforming Growth Factor-β (TGF-β) and TNF-α in promoting splenocyte apoptosis [123]. …”