Host ICAMs play a role in cell invasion by Mycobacterium tuberculosis and Plasmodium falciparum

• DOI: 10.1038/ncomms7049
• Publication Date: 2015-01-14T11:53:32Z
• Authors: Kuhulika Bhalla; Monika Chugh; Sonali Mehrotra; Sumit Rathore; Sultan Tousif; Ved Prakash Dwivedi; Prem Prakash; Sachin Kumar Samu...; Sushil Kumar; Dhiraj Kumar Singh; Swapnil Ghanwat; Dhiraj Kumar; Gobardhan Das; Asif Mohmmed; Pawan Malhotra; Anand Ranganathan
• Keywords: Mice, Inbred BALB C; 0303 health sciences; Erythrocytes; Merozoites; Plasmodium falciparum; Mycobacterium tuberculosis; Intercellular Adhesion Molecule-1; Cell Line; Protein Structure, Tertiary; 3. Good health; 03 medical and health sciences; Two-Hybrid System Techniques; Host-Pathogen Interactions; Protein Interaction Mapping; Animals; Humans; Tuberculosis; Female; Malaria, Falciparum; Protein Multimerization; Cell Adhesion Molecules; Protein Binding

Intercellular adhesion molecules (ICAMs) belong to the immunoglobulin superfamily and participate in diverse cellular processes including host-pathogen interactions. ICAM-1 is expressed on various cell types including macrophages, whereas ICAM-4 is restricted to red blood cells. Here we report the identification of an 11-kDa synthetic protein, M5, that binds to human ICAM-1 and ICAM-4, as shown by in vitro interaction studies, surface plasmon resonance and immunolocalization. M5 greatly inhibits the invasion of macrophages and erythrocytes by Mycobacterium tuberculosis and Plasmodium falciparum, respectively. Pharmacological and siRNA-mediated inhibition of ICAM-1 expression also results in reduced M. tuberculosis invasion of macrophages. ICAM-4 binds to P. falciparum merozoites, and the addition of recombinant ICAM-4 to parasite cultures blocks invasion of erythrocytes by newly released merozoites. Our results indicate that ICAM-1 and ICAM-4 play roles in host cell invasion by M. tuberculosis and P. falciparum, respectively, either as receptors or as crucial accessory molecules.